ArticlePDF Available

The Penumbra System: A Mechanical Device for the Treatment of Acute Stroke due to Thromboembolism

Authors:

Abstract and Figures

Data from recent reports have indicated that mechanical thrombectomy may have potential as a treatment for acute ischemic stroke. The purpose of this study was to assess the safety and performance of the Penumbra System (PS): a novel mechanical device designed to reduce clot burden in acute stroke due to large-vessel occlusive disease. A prospective, single arm, independently monitored and core laboratory adjudicated trial enrolled subjects with an acute neurologic deficit consistent with acute stroke, presenting within 8 hours of symptom onset and an angiographically verified occlusion (Thrombolysis in Myocardial Infarction [TIMI] grade 0 or 1) of a treatable intracranial vessel. The primary end point was revascularization of the target vessel to TIMI grade 2 or 3. Secondary end points were the proportion of subjects who achieved a modified Rankin Scale (mRS) score of 2 or less or a 4-point improvement on the National Institutes of Health Stroke Scale (NIHSS) score at 30-day follow-up, as well as all-cause mortality. Twenty-three subjects were enrolled, and 21 target vessels were treated in 20 subjects by the PS. At baseline, mean age was 60 years, mean mRS score was 4.6, and mean NIHSS score was 21. Postprocedure, all 21 of the treated vessels (100%) were successfully revascularized by the PS to TIMI 2 or 3. At 30-day follow-up, 9 subjects (45%) had a 4-point or more NIHSS improvement or an mRS of 2 or less. The all-cause mortality rate was 45% (9 of 20), which is lower than expected in this severe stroke cohort, where 70% of the subjects at baseline had either an NIHSS score of more than 20 or a basilar occlusion. Thus, early clinical experience suggests that the PS allows revascularization in certain subjects experiencing acute ischemic stroke.
Content may be subject to copyright.
ORIGINAL
RESEARCH
The Penumbra System: A Mechanical Device for
the Treatment of Acute Stroke due to
Thromboembolism
A. Bose
H. Henkes
K. Alfke
W. Reith
T.E. Mayer
A. Berlis
V. Branca
S. Po Sit,
for the Penumbra
Phase 1 Stroke Trial
Investigators
BACKGROUND AND PURPOSE: Data from recent reports have indicated that mechanical thrombectomy
may have potential as a treatment for acute ischemic stroke. The purpose of this study was to assess
the safety and performance of the Penumbra System (PS): a novel mechanical device designed to
reduce clot burden in acute stroke due to large-vessel occlusive disease.
MATERIALS AND METHODS: A prospective, single arm, independently monitored and core laboratory
adjudicated trial enrolled subjects with an acute neurologic deficit consistent with acute stroke,
presenting within 8 hours of symptom onset and an angiographically verified occlusion (Thrombolysis
in Myocardial Infarction [TIMI] grade 0 or 1) of a treatable intracranial vessel. The primary end point was
revascularization of the target vessel to TIMI grade 2 or 3. Secondary end points were the proportion
of subjects who achieved a modified Rankin Scale (mRS) score of 2 or less or a 4-point improvement
on the National Institutes of Health Stroke Scale (NIHSS) score at 30-day follow-up, as well as all-cause
mortality.
RESULTS: Twenty-three subjects were enrolled, and 21 target vessels were treated in 20 subjects by
the PS. At baseline, mean age was 60 years, mean mRS score was 4.6, and mean NIHSS score was
21. Postprocedure, all 21 of the treated vessels (100%) were successfully revascularized by the PS to
TIMI 2 or 3. At 30-day follow-up, 9 subjects (45%) had a 4-point or more NIHSS improvement or an
mRS of 2 or less. The all-cause mortality rate was 45% (9 of 20), which is lower than expected in this
severe stroke cohort, where 70% of the subjects at baseline had either an NIHSS score of more than
20 or a basilar occlusion.
CONCLUSION: Thus, early clinical experience suggests that the PS allows revascularization in certain
subjects experiencing acute ischemic stroke.
C
urrent thrombolytic therapy in acute ischemic stroke is
often not effective or can be difficult to administer within
the indicated brief treatment window of 3 hours from symp-
tom onset. The average time from stroke onset to arrival in an
emergency department is between 3 and 6 hours. Mortality
rates associated with occlusions of the basilar artery, internal
carotid artery (ICA) terminus, and M1 segment of the middle
cerebral artery (MCA) are particularly high despite best avail-
able medical therapy.
1-3
The paucity of safe and effective treat
-
ment strategies presents a profound unmet clinical need in the
management of this prevalent and debilitating disease. Sub-
stantial evidence in the published literature suggests that early
and safe revascularization of the primary occlusion correlates
with improved clinical outcome.
4
The probable basis for this
correlation is that, although some brain tissue experiences
near immediate and irreversible infarction during acute
stroke, there remains a region of ischemic penumbra sur-
rounding this area where at-risk tissue can be salvaged.
4
Therefore, if timely revascularization can be effected and
reperfusion established, then damage to the penumbral region
could be reversed, resulting in a diminished neurologic deficit,
reduced stroke-related mortality and morbidity, and im-
proved clinical outcome.
With the advent of endovascular therapy, a number of al-
ternative mechanical approaches have shown promise in re-
storing blood flow in an occluded artery in acute ischemic
stroke.
5,6
The Penumbra System (PS; Penumbra, Alameda,
Calif) is a new embolectomy device specifically designed to
remove the thrombus in acute ischemic stroke secondary to
large vessel thromboembolism. The device removes the
thrombus through 2 mechanisms: aspiration and extraction.
The PS is composed of 3 main components: a reperfusion
catheter, separator, and thrombus removal ring (Fig 1). For
aspiration, the reperfusion catheter is used in parallel with the
separator and an aspiration source to separate the thrombus
and aspirate it from the occluded vessel. If residual thrombus
remains after revascularization with aspiration, the thrombus
removal ring is used to directly engage and remove the
thrombus.
Materials and Methods
A prospective, multicenter, single-arm trial was designed to assess the
safety and performance of the PS in acute ischemic stroke. The pro-
tocol called for up to 30 subjects with acute ischemic stroke to be
enrolled at 6 international centers for treatment with the PS within 8
hours of symptom onset; however, only 23 subjects were enrolled due
to a higher than expected revascularization rate (100%). The primary
end point was the ability of the PS to revascularize the affected vessel
to Thrombolysis in Myocardial Infarction (TIMI) 2 or greater after
use of the system.
7
The secondary end points were the proportion of
subjects who achieved a modified Rankin Scale (mRS) score of 2 or
Received October 11, 2007; accepted after revision March 5, 2008.
From Lenox Hill Hospital (A.B.), New York, NY; Robert Janker Klinik (H.H.), Bonn, Germany;
University of Kiel Medical Center (K.A.), Kiel, Germany; Universita¨tsklinikum des Saarlandes
(W.R.), Homburg/Saar, Germany; Universita¨t Mu¨nchen Klinikum (T.E.M.), Munich, Germany;
Universita¨t Hospital (A.B.), Freiburg, Germany; Ospedale Maggiore Milano (V.B.), Milan,
Italy; and Penumbra Inc (A.B., S.P.S.), San Leandro, Calif.
Please address correspondence to Siu Po Sit, Penumbra, Inc, 1351 Harbor Bay Pkwy,
Alameda, CA 94502; e-mail: ssit@penumbrainc.com
DOI 10.3174/ajnr.A1110
INTERVENTIONAL ORIGINAL RESEARCH
AJNR Am J Neuroradiol 29:1409 –13 Aug 2008 www.ajnr.org 1409
less or a 4-point improvement on the National Institutes of Health
Stroke Scale (NIHSS) at 30 days postprocedure. The 30-day all-cause
mortality rate was also assessed.
Inclusion and Exclusion Criteria
The main entry criteria for the study were as follows: 1) clinical signs
consistent with acute ischemic stroke; 2) age 18 years or older; 3) a
score of TIMI 0 or 1 in a vessel accessible by the PS; and 4) presenta-
tion within 8 hours of stroke symptom onset (if presenting within 3
hours of stroke symptom onset, the subject must have been ineligible
for or refractory to treatment with intravenous [IV] recombinant
tissue plasminogen activation [rtPA]). Principal exclusion criteria for
enrollment were as follows: subjects who were at risk of bleeding,
vessels that were too tortuous for access by the PS, and subjects with
severe, uncontrolled hypertension. Women who were pregnant were
also excluded.
Subject Selection
Subjects presenting with stroke symptoms were screened to deter-
mine whether they met entry criteria for the study. After obtaining
signed informed consent, all of the eligible subjects were evaluated for
neurologic and functional status, and an angiographic assessment of
the suspected vascular occlusion was obtained. An arterial access pro-
cedure was performed by using standard percutaneous techniques
under systemic heparin and general anesthesia per the local institu-
tional standard of care. For subjects without thrombolytic therapy
onboard, heparin was given IV at a dose of 5000 IU bolus followed by
a continuous infusion at 2000 IU/h to maintain an activated clotting
time of 250 seconds or more. For subjects who had received throm-
bolytic therapy, it was given at a dose of 2000 IU bolus followed by a
continuous infusion at 1000 IU/h.
Treatment Procedures
Four-vessel digital subtraction angiography was used to define the
angioarchitecture of the occluded vascular segment. An appropriate
guide catheter was then brought into position in the occluded target
vessel territory to enable access by the reperfusion catheter. All of the
components of the PS are deliverable via a 6F standard guide catheter.
A subject was considered enrolled into the study when the reperfusion
catheter was deployed from the guide catheter to the site of occlusion.
Once the appropriate position was achieved proximal to the clot, the
guidewire was removed from the reperfusion catheter, and the sepa-
rator was advanced through the reperfusion catheter. The aspiration
pump was then turned on to initiate revascularization. Reduction of
the clot burden by aspiration was accomplished by connecting the
reperfusion catheter to the aspiration pump, which generated a vac-
uum of 20 inches Hg. A continuous aspiration-debulking process
was facilitated by advancing and withdrawing the separator through
the reperfusion catheter into the proximal end of the clot. If the
thrombus remained, a second accessory method of direct mechanical
retrieval by the thrombus removal ring was used to augment revascu-
larization. Thrombus extraction by using the thrombus removal ring
was accomplished by engaging the clot proximally and extracting the
clot under flow arrest conditions by inflating a proximal balloon
guide catheter. If the PS was successful in revascularization of the
target vessel to TIMI 2 or better, no additional interventions were
performed. Administration of anticoagulants and antiplatelets were
suspended for 24 hours posttreatment. If the subject experienced
symptoms that appeared to be indicative of an intracranial hemor-
rhage (ICH; neurologic deterioration or alteration in function), an
emergent CT scan or MR imaging was conducted. A follow-up CT
was required 14 days after the initial emergent CT.
Study End Points
The primary end point for this study was incidence of revasculariza-
tion of the target vessel as defined by achieving TIMI 2 or 3 flow after
use of the PS (Fig 2).
7
Each investigator made an initial assessment of
TIMI flow in the target vessel preprocedure and postprocedure. Pre-
procedure and postprocedure angiograms were sent to an indepen-
dent core laboratory to make a final determination on TIMI flow.
Fig 1. Schematic diagram of the Penumbra device.
Fig 2. Angiographic illustration of a target vessel before (A) and after (B) treatment by the PS. This patient was a 66-year-old man who presented 3 hours from symptom onset with an
NIHSS score of 24, which improved to 8 at 24 hours after revascularization by the PS. He continued to recover with a 30-day NIHSS score of 2 and an mRS of 1.
1410 Bose AJNR 29 Aug 2008 www.ajnr.org
Data based on core laboratory assessments were used for final
analysis.
Results
Twenty-three subjects at 6 international centers were enrolled
with 21 vessels treated by the PS. Three enrolled subjects were
not treated due to vessel tortuosity, resulting in an access rate
of 87% (20 of 23). Among the 20 subjects, 8 (40%) were
women. They had a mean age of 60 18 ( SD), baseline mRS
of 4.6 0.8, and NIHSS score of 21 8. Eleven (45%) had a
baseline NIHSS score of more than 20. Fifty percent of the
subjects (10 of 20) presented more than 3 hours from symp-
tom onset. Of the remaining 50% who presented within 3
hours, 6 were refractory to rtPA therapy, and 4 were not eligi-
ble for thrombolytic therapy. Among the 21 vessels treated by
the PS, 7 (33%) were ICA, 5 (24%) were MCA, and 9 (43%)
were basilar arteries. Fourteen (70%) of the subjects had either
a baseline NIHSS score of more than 20 or a basilar occlusion.
The 3 subjects who were enrolled but not treated were due to
the inability of the PS to access the target lesions. Two of these
subjects presented with left M1 occlusion and 1 with a site of
primary occlusion at the right ICA supraclinoid region. There
were no reports of adverse events during the procedures. All 3
of the subjects were discharged to either a rehab center or a
nursing home. Two of the subjects survived through the 30-
day follow-up, of which one showed improvement in the
NIHSS and the other remained stable. The third subject with
the left M1 occlusion showed a small, asymptomatic ICH in
the infarcted area from a follow-up CT at 3 days postproce-
dure. It did not progress, and her NIHSS score remained stable
at 19 (from a baseline of 22). This subject died at 32 days
postprocedure from worsening of pre-existing heart failure,
unrelated to the procedure or the device. All of the treated
target vessels were either TIMI 0 (19 of 21) or TIMI 1 (2 of 21)
before treatment with the PS, and all were successfully revas-
cularized to TIMI 2 or 3 after use of the Penumbra stroke
system (21 of 21; Table 1).
In the study, additional interventions with intra-arterial
(IA) rtPA were performed in 9 subjects after use of the PS, with
doses ranging from 10 to 45 mg given as a bolus. The main
reason cited by the investigators for using IA rtPA was the
intention to better the score from TIMI 2 due to evidence of
vessel occlusion in the vasculature distal to the revascularized
target vessel. The TIMI scores summarized above were re-
corded before any adjunctive treatment had been initiated, at a
time when revascularization by the PS alone was considered
complete. The secondary end points were the proportion of
subjects who achieved an mRS of 2 or less or a 4-point im-
provement on the NIHSS at 30-day follow-up, as well as all-
cause mortality.
In the treated subjects, 45% (9 of 20) of subjects with 30-
day data achieved at least a 4-point improvement of NIHSS or
an mRS of 2 or less. A total of 9 subjects had an improvement
of 4 or more points on the NIHSS score, and 7 subjects had an
mRS of 2 or less. Results from a subgroup analysis indicate that
subjects with a baseline NIHSS score of more than 20 tended
to have lower probability of a good outcome at 30 days post-
procedure (Fig 3).
Of the 20 enrolled subjects who were treated by the system,
9 died within the 30-day follow-up period, resulting in an
all-cause mortality of 45% (9 of 20). This rate is lower than
expected in this severe stroke cohort, where at baseline, 70% of
the subjects had either an NIHSS score of more than 20 or a
basilar occlusion (Fig 4).
1-3
None of these deaths were related
to the study device. The most frequently cited cause of death
for these subjects was hemorrhagic conversion of a region of
infarction and cerebral edema secondary to infarction.
Two procedural adverse events were reported from 21 pro-
cedures. One subject experienced a groin hematoma at the
puncture site, which was treated with a transfusion and re-
solved. Another subject experienced an intraprocedural sub-
arachnoid hemorrhage. The hemorrhage did not result in any
deterioration of the subject’s neurologic condition and re-
solved with no action taken. There were no other reports of
arterial perforation, dissection, or embolization of a previ-
ously uninvolved territory of the brain.
There was a total of 8 reported cases of ICH, of which 2
were symptomatic as defined by CT evidence of a bleeding
event and a 4-point deterioration on the NIHSS score.
8
In7of
the 8 cases of ICH, IA thrombolytics were administered after
use of the PS. In 1 of the 8 cases, IV thrombolytics were given
before treatment with the PS. Among the 8 cases of hemor-
rhage, 1 was thought to have been caused by the device (see
TIMI scores (core laboratory adjudicated)
Variable
Baseline
(N 21), % (n/N)
Posttreatment
(N 21), % (n/N)
TIMI 0 90 (19/21) 0 (0/21)
TIMI 1 10 (2/21) 0 (0/21)
TIMI 2 0 (0/21) 48 (10/21)
TIMI 3 0 (0/21) 52 (11/21)
Note:—Twenty-one target vessels were treated in 20 subjects. TIMI indicates Thrombol-
ysis in Myocardial Infarction.
Fig 3. Subjects outcome based on baseline NIHSS scores.
Fig 4. A comparison of the observed and expected mortality rates for the entire study
cohort and after stratification by location of the target vessel. The expected rates were
derived from historical rates from the natural history of the disease reported in the
literature, prorated to the proportion of target vessel locations treated in this study (see
References 1–3).
AJNR Am J Neuroradiol 29:1409 –13 Aug 2008 www.ajnr.org 1411
above description of intraprocedural subarachnoid hemor-
rhage). Adjunctive IA thrombolytic therapy was associated
with a higher incidence of hemorrhage.
Discussion
Current medical practice offers physicians various treatment
strategies in the management of acute ischemic stroke. Unfor-
tunately, many treatment modalities face limitations that pre-
vent substantive improvements of stroke-related morbidity
and mortality.
The National Institute of Neurological Disorders and
Stroke study found that subjects experienced the greatest ben-
efit from treatment with rtPA if treatment was initiated within
3 hours of stroke symptom onset.
9
At 3 months, rtPA-treated
subjects were 30% more likely to have minimal or no disability
compared with the placebo-treated subjects. Subjects in the
treatment group did experience a higher rate of symptomatic
ICH (6.4% versus 0.6%); however, the investigators showed
the benefits of the treatment outweighed the risk. Because sub-
jects are at a greater risk for hemorrhage with thrombolytic use
after 3 hours of symptom onset, the study only enrolled those
subjects who presented within 3 hours from symptom onset
who had minimal bleeding-complication risk factors.
IV administration of thrombolytic agents requires a high
dose to be given to the subject that may increase the risk of
ICH. The Prolyse in Acute Cerebral Thromboembolism II
Trial sought to assess whether local, IA administration of
prourokinase at the site of the thrombus would be safe and
effective for the treatment of ischemic stroke.
10
Subjects pre
-
senting within 6 hours of stroke symptom onset and with oc-
clusions of the MCA were enrolled, and subjects were ran-
domly assigned to receive 9-mg IA recombinant prourokinase
(r-proUK) plus heparin or heparin alone (control). At 90 days,
40% of r-proUK-treated subjects and 25% of control subjects
had an mRS of 2 or less. Mortality for the 2 groups was equiv-
alent (25% in the treatment arm versus 27% in the control
arm), and the symptomatic ICH rate was 10% for the treat-
ment group and 2% for the control group.
In an attempt to reduce systemic adverse effects associated
with the use of thrombolytic agents, focus has shifted to me-
chanical rather than pharmaceutical means of recanalizing the
site of primary occlusion in subjects experiencing acute isch-
emic stroke. Only one mechanical device, approved in a safety
study, is available on the market in the United States and Eu-
rope for revascularization of occlusions caused by acute isch-
emic stroke (Merci Retriever; Concentric Medical, Mountain
View, Calif).
11-13
Published data for the Merci Retriever based
on 141 treated subjects showed a revascularization rate (TIMI
2/3 flow) of 48% with a clinically significant procedure-related
adverse event rate of 7.1% (10 of 141).
11
Eleven subjects
(7.8%) experienced a symptomatic ICH within 24 hours, and
27.7% had asymptomatic ICH. At 90 days, 43.5% of subjects
died, and 27.7% of subjects had a good outcome (mRS 2). In
the Multi Mechanical Embolus Removal in Cerebral Ischemia
Trial, where a combined therapy of the Merci Retriever and
rtPA treatment (IV/IA) was assessed, the rate of revasculariza-
tion was increased to 69.0%, and mortality was reduced to
30.6% at 3 months.
12
However, this was associated with an
increase in symptomatic ICH to 9.0% and an increase in the
asymptomatic ICH rate to 29.7%. Similarly, in the Interven-
tional Management of Stroke I Trial, a combined therapy of IV
and IA rtPA resulted in a protocol-defined revascularization
rate of 56%, a symptomatic ICH rate of 6.3%, and an asymp-
tomatic ICH rate of 42.5%.
By comparison, in this small cohort of subjects, the PS was
able to revascularize the site of primary occlusion in all of the
treated subjects enrolled into the study, resulting in a revascu-
larization rate of 100%, of which 45% had met the secondary
end point of achieving a 4-point improvement on the NIHSS
or an mRS of 2 or less at 30 days postprocedure. This was
associated with a device or procedure-related serious adverse
event rate of 10% and an all-cause mortality rate of 45%.
Eight subjects were observed to have ICH in this study, of
which 2 (10%) were symptomatic and 6 (30%) were asymp-
tomatic. The risk of cerebral hemorrhage secondary to the use
of IA rtPA therapy is controversial in the literature.
8,14-16
In
this small cohort of patients, the observation of ICH was asso-
ciated with the use of additional IA rtPA as adjunctive therapy
to the PS to reduce the clot burden in distal branches beyond
the site of primary occlusion. Additional studies may be war-
ranted to better define the optimal use of adjunctive IA lytic
therapy to reduce clot burden at the site of primary occlusion
and to improve distal perfusion after the site of primary occlu-
sion has been revascularized.
The device safety and revascularization success of the PS
appears promising in this early clinical experience. In addi-
tion, the neurologic and functional improvement noted in
some subjects is encouraging in this patient cohort where 70%
of the subject at baseline had either an NIHSS score of more
than 20 or a basilar occlusion. Further investigation seems
warranted to better define the safety and efficacy of the PS in
acute ischemic stroke.
Conclusions
In this prospective, phase 1, single arm trial, the PS allows
revascularization of occluded intracranial large vessels in a
small stroke cohort who presented within 8 hours from symp-
tom onset. This early clinical experience suggests that the PS
may have potential as treatment for acute ischemic stroke sec-
ondary to large-vessel thromboembolism and that further
clinical testing is warranted.
Clinical Investigators
Participating centers principal investigator (PI) and coinves-
tigator(s) (Co) in order of enrollment (n): Robert Janker
Klinik, Bonn, Germany: Hans Henkes, MD (PI), and Stefan
Lowens, MD (Co) (6); University of Kiel Medical Center, Kiel,
Germany: Prof Olav Jansen, MD (PI), and Karsten Alfke, MD
(Co) (5); Universita¨tsklinikum des Saarlandes, Homburg/
Saar, Germany: Prof Wolfgang Reith, MD (PI), Prof Klaus
Fassbender, MD (Co), Iris Grunwald, MD (Co), Joearg Oster-
hage, MD (Co), Panagiotis Papanagiotou, MD (Co), and Er-
dem Orberk, MD (Co) (5); Universita¨t Mu¨nchen Klinikum,
Munich, Germany: Prof Thomas E. Mayer, MD (PI),
Stephanie Muller-Schunk, MD (Co), Prof Martin Wiesmann,
MD (Co), Prof Hartmut Bruckmann, MD (Co), Klaus Seelos,
MD (Co), Gunther Fesl, MD (Co), Markus Holtmannspotter,
MD (Co), Prof Martin Dichgans, MD (Co), and Yvonne Me-
wald, MD (Co) (3); Universita¨t Hospital, Freiburg, Germany:
Ansgar Berlis, MD (PI), Prof Martin Schumacher, MD (Co),
1412 Bose AJNR 29 Aug 2008 www.ajnr.org
Wolf-Dirk Niesen, MD (Co), and Andreas Hetzel, MD (Co)
(2); and Ospedale Maggiore Milano, Milan, Italy: Vincenzo
Branca, MD (PI) (2).
Acknowledgments
We thank Prof Dr Michael Knauth and the George-August-
University, Bereich Humanmedizin, Go¨ttingen, Germany, for
their invaluable services as the angiographic core laboratory in
this study.
References
1. Jansen O, von Kummer R, Forsting M, et al. Thrombolytic therapy in acute
occlusion of the intracranial internal carotid artery bifurcation. AJNR Am J
Neuroradiol 1995;16:1977– 86
2. Brandt T, von Kummer R, Muller-Kuppers M, et al. Thrombolytic therapy of
acute basilar artery occlusion. Stroke 1996;27:875– 81
3. Eckert B, Koch C, Thomalla G, et al. Aggressive therapy with intravenous
abcizimab and intra-arterial rtPA and additional PTA/stenting improves
clinical outcome in acute vertebrobasilar occlusion: combined local fibrino-
lysis and intravenous abciximab in acute vertebrobasilar stroke treatment
(FAST): results of a multicenter study. Stroke 2005;36:1160 65
4. Jansen O, Schellinger P, Fiebach J, et al. Early revascularization in acute isch-
emic stroke saves tissue at risk defined by MRI. Lancet 1997;353:2036 –37
5. Leary M, Saver S, Gobin Y, et al. Beyond tissue plasminogen activator: me-
chanical intervention in acute stroke. Ann Emerg Med 2003;41:838 46
6. Gomez CR, Orr SC, Soto RD. Neuroendovascular rescue: Interventional treat-
ment of acute ischemic stroke. Curr Treat Options Cardiovasc Med 2002;4:405–19
7. Thrombolysis in Myocardial Infarction (TIMI) Trial: phase 1 findings TIMI
Study Group. N Engl J Med 1985;312:932–36
8. Khatri P, Wechsler LR, Broderick JP. Intracranial hemorrhage associated with
revascularization therapies. Stroke 2007;38:431– 40
9. The National Institute of Neurological Disorders and Stroke t-PA Stroke Study
Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med
1995;333:1581– 87
10. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute
ischemic stroke. The PROACT II Study: a randomized controlled trial. JAMA
1999;282:2003–11
11. Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embo-
lectomy in acute ischemic stroke: results of the MERCI trial. Stroke
2005;36:1432–38
12. Smith WS. Safety of mechanical thrombectomy and intravenous tissue plas-
minogen activator in acute ischemic stroke. Results of the multi Mechanical
Embolus Removal in Cerebral Ischemia (MERCI) trial, part I. AJNR Am J
Neuroradiol 2006;27:1177– 82
13. Gobin YP, Starkman S, Duckwiler GR, et al. MERCI 1: a phase 1 study of me-
chanical embolus removal in cerebral ischemia. Stroke 2004;35:2848–54
14. Ogawa A, Mori E, Minematsu K, et al. Randomized trial of intraarterial infu-
sion of urokinase within 6 hours of middle cerebral artery stroke. The middle
cerebral artery embolism local fibrinolytic intervention trial (MELT) Japan.
Stroke 2007;38:2633–39
15. Saver JL. Intra-arterial fibrinolysis for acute ischemic stroke. The message of
MELT. Stroke 2007;38:2627–28
16. IMS Trial Investigators. Combined intravenous and intra-arterial revascular-
ization for acute ischemic stroke: the interventional management of stroke
study. Stroke 2004;35:904–11
AJNR Am J Neuroradiol 29:1409 –13 Aug 2008 www.ajnr.org 1413
... Here, blood supply is insufficient to maintain ion gradients across the neuronal plasma membrane and loss of neuronal function is quickly followed by neuronal death. In surrounding areas, often referred to as the 'penumbra', perfusion levels are higher, between 10 and 35 mL/100 g/min, because of blood supply from adjacent arteries [2]. Here, neurons initially remain structurally intact and viable, but activity is impeded by widespread failure of synaptic transmission. ...
... Synaptic failure in the penumbra is one of the early consequences of mild-to-moderate cerebral ischemia [3,4]. The penumbra is viable for at least several hours, depending on remaining perfusion levels, and may be salvaged by timely restoration of perfusion, resulting in improved patient outcomes [2]. If reperfusion is not established in time, the neurons in the penumbra undergo transition to irreversible neuronal damage [5][6][7]. ...
Article
Full-text available
In the penumbra of a brain infarct, neurons initially remain structurally intact, but perfusion is insufficient to maintain neuronal activity at physiological levels. Improving neuronal recovery in the penumbra has large potential to advance recovery of stroke patients, but penumbral pathology is incompletely understood, and treatments are scarce. We hypothesize that low activity in the penumbra is associated with apoptosis and thus contributes to irreversible neuronal damage. We explored the putative relationship between low neuronal activity and apoptosis in cultured neurons exposed to variable durations of hypoxia or TTX. We combined electrophysiology and live apoptosis staining in 42 cultures, and compared effects of hypoxia and TTX silencing in terms of network activity and apoptosis. Hypoxia rapidly reduced network activity, but cultures showed limited apoptosis during the first 12 h. After 24 h, widespread apoptosis had occurred. This was associated with full activity recovery observed upon reoxygenation within 12 h, but not after 24 h. Similarly, TTX exposure strongly reduced activity, with full recovery upon washout within 12 h, but not after 24 h. Mean temporal evolution of apoptosis in TTX-treated cultures was the same as in hypoxic cultures. These results suggest that prolonged low activity may be a common factor in the pathways towards apoptosis.
... Stent retriever devices, such as the Trevo TM and Solitaire TM , are used to "grab" the clot by mechanical interference, allowing the clot to be pulled out along with the catheter [15,16]. Aspiration guide catheters, such as the Penumbra, provide suction to assist in removal [2,17,18]. Often an aspiration guide is used in combination with a stent retriever. ...
Article
Full-text available
Strokes are among the leading causes of death worldwide. Ischemic stroke, due to plaque or other buildup blocking blood flow to the brain, is the most common type. Although ischemic stroke is treatable, current methods have severe shortcomings with high mortality rates. Clot retrieval devices, for example, can result in physically damaged vessels and death. This study aims to create blood clots that are representative of those found in vivo and demonstrate a new method of removing them. Static blood clots were formed using a 9:1 ratio of whole sheep blood and 2.45% calcium chloride solution. This mixture was heated in a water bath at 37 °C for approximately one hour until solidified. Following clot solidification, human plasmin was introduced by various methods, including soaking, injection, and membrane perfusion, and the resulting dissolution percentages were determined. Different clot types, representative of the wide range found physiologically, were also manufactured and their dissolution characteristics evaluated. A method to reproducibly create blood clots, characteristic of those found in vivo, is essential for the production of stroke retrieval devices that can efficiently and effectively remove clots from patients with low mortality rates and little/no damage to the surrounding vessels.
... The procedure of mechanical thrombectomy can be used for the removal of blood clots obstructing larger blood vessels, in order to increase the therapeutic window by up to 24 hours [33]. There are currently two types of mechanical thrombectomy procedures, that either use stent retrievers like Solitaire (Meditronic) and Trevo (Stryker), or aspiration catheters such as Penumbra [5,23], which are used separately or together. ...
Preprint
Full-text available
Acute ischemic stroke, the second leading cause of death worldwide, results from occlusion of a cerebral artery by a blood clot. Application of cyclic aspiration using an aspiration catheter is a current therapy for the removal of lodged clots. In this study, we perform finite element simulations to analyze deformation of long clots, having length to radius ratio of 2 to 10, which corresponds to clot-length of 2.85–14.25 mm, under peak-to-peak cyclic aspiration pressures of 10 to 50 mmmHg, and frequencies of 0.5, 1 and 2 Hz. Our computational system comprises of a nonlinear viscoelastic solid clot, a hyperelastic artery, and a nonlinear viscoelastic cohesive zone, the latter modeling the clot–artery interface. We observe that clots having length-to-radius ratio approximately greater than two separate from the inner arterial surface somewhere between the axial and distal ends, irrespective of the cyclic aspiration loading conditions. The stress distribution within the clot shows large tensile stresses in the clot interior, indicating the possibility of simultaneous fragmentation of the clot. Thus, this study shows us the various failure mechanisms simultaneously present in the clot during cyclic aspiration. Similarly, the stress distribution within the artery implies a possibility of endothelial damage to the arterial wall near the end where the aspiration pressure is applied. This framework provides a foundation for further investigation to clot fracture and adhesion characterization.
... Thereafter, a continuous aspiration and debulking process ensued using the Penumbra Separator. Subsequently, extraction was then performed using the thrombus extracting ring, which was deployed under proximal flow arrest [15]. The Penumbra Pivotal Stroke trial reported a recanalization rate of 81%, the procedural event rate was 12.8%, out of which 2.4% were serious events. ...
Article
Full-text available
Stroke is a leading cause of serious long-term disability in the US. Endovascular therapy (EVT), in the form of mechanical thrombectomy, is now a standard of care for patients with acute ischemic stroke with a large vessel occlusion. This article reviews the evolution of EVT in the management of acute ischemic stroke and how it has led to the concept of tissue window over the widely publicized time window.
Chapter
Translating laboratory discoveries into successful therapeutics can be difficult. Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases. It introduces the reader to the key concepts underpinning trials in the neurosciences. This volume tackles the challenges of developing therapies for neurologic disorders from measurement of agents in the nervous system to the progression of clinical signs and symptoms through illustrating specific study designs and their applications to different therapeutic areas. Clinical Trials in Neurology covers key issues in Phase I, II and III clinical trials, as well as post-marketing safety surveillance. Topics addressed include regulatory and implementation issues, outcome measures and common problems in drug development. Written by a multidisciplinary team, this comprehensive guide is essential reading for neurologists, psychiatrists, neurosurgeons, neuroscientists, statisticians and clinical researchers in the pharmaceutical industry.
Article
Full-text available
BACKGROUND The world of medicine has grown through the strength and determination of pioneers who developed an understanding of many diseases affecting humans or inventing new diagnostic and/or therapeutic procedures. 1 Of these, endovascular surgical neuroradiology is a subspecialty that offers minimally invasive techniques instead of surgical approaches. 2 Over the years, the terms endovascular neurosurgery, intervention-al neurology, interventional neuroradiology, neuro-interven-tional radiology, neuro-endovascular surgery, endovascular surgical neurology and endovascular surgical neuroradiology have been used interchangeably. 3 In the past decades, endo-vascular surgical neuroradiology has transformed rapidly through advances in devices and techniques. There are numerous applications for endovascular surgical neuroradiolo-gy such as diagnostic angiography of brain and spine, aneu-rysm embolization, embolization treatment for arteriovenous malformations (AVMs) and tumors of head/neck and spine, thrombectomy and intra-arterial infusion of medications (ve-rapamil for vasospasm, WADA for provocative testing). 4-10 J VIN Journal of Vascular and Interventional Neurology Abstract Background-Endovascular surgical neuroradiology uses minimally invasive techniques to treat cerebrovascular diseases. Although radiologists and neurosurgeons made significant contribution to this field, the role of neurologists has been increased over the past few decades.
Article
Full-text available
BACKGROUND The world of medicine has grown through the strength and determination of pioneers who developed an understanding of many diseases affecting humans or inventing new diagnostic and/or therapeutic procedures. 1 Of these, endovascular surgical neuroradiology is a subspecialty that offers minimally invasive techniques instead of surgical approaches. 2 Over the years, the terms endovascular neurosurgery, intervention-al neurology, interventional neuroradiology, neuro-interven-tional radiology, neuro-endovascular surgery, endovascular surgical neurology and endovascular surgical neuroradiology have been used interchangeably. 3 In the past decades, endo-vascular surgical neuroradiology has transformed rapidly through advances in devices and techniques. There are numerous applications for endovascular surgical neuroradiolo-gy such as diagnostic angiography of brain and spine, aneu-rysm embolization, embolization treatment for arteriovenous malformations (AVMs) and tumors of head/neck and spine, thrombectomy and intra-arterial infusion of medications (ve-rapamil for vasospasm, WADA for provocative testing). 4-10 J VIN Journal of Vascular and Interventional Neurology Abstract Background-Endovascular surgical neuroradiology uses minimally invasive techniques to treat cerebrovascular diseases. Although radiologists and neurosurgeons made significant contribution to this field, the role of neurologists has been increased over the past few decades.
Chapter
The practice of modern medicine relies on a combination of compassionate care and expert knowledge developed through rigorous research principles and scientific discoveries. This puts the impetus on physicians to guide their clinical practice based on clinical expertise, patient values, and the best research evidence available via critical appraisal of study methods for validity of results. The authors of this chapter provide examples of how research across this continuum has contributed to current clinical practice: from new diagnostic and predictive tools improving management of PE and stroke to advances in robotics providing opportunities for new surgical procedures.
Article
The advent of endovascular therapy for acute large vessel occlusion has revolutionized stroke treatment. Timely access to endovascular therapy, and the ability to restore intracranial flow in a safe, efficient, and efficacious manner has been critical to the success of the thrombectomy procedure. The stentriever has been a mainstay of endovascular stroke therapy, and current guidelines recommend the usage of stentrievers in the treatment of large vessel occlusion stroke. Despite the success of existing stentrievers, there continues to be significant development in the field, with newer stentrievers attempting to improve on each of the three key aspects of the thrombectomy procedure. Here, we elucidate the technical requirements that a stentriever must fulfill. We then review the basic variables of stent design, including the raw material and its form, fabrication method, geometric configuration, and further additions. Lastly, a selection of stentrievers from successive generations are reviewed using these engineering parameters, and clinical data is presented. Further avenues of stentriever development and testing are also presented.
Article
Mechanical thrombectomy is established as standard of care in the management of acute ischemic stroke due to large vessel occlusion and evidence-based guidelines for mechanical thrombectomy have been defined. As research continues to further expand the eligibility criteria for thrombectomy and the number of thrombectomy procedures increase worldwide, there is also growing focus on innovation of thrombectomy devices, procedural techniques, and related outcomes. Thrombectomy primarily involves use of stent retrievers and distal aspiration techniques, but variations and different combinations of techniques have been reported. As this is a rapidly evolving area in stroke management, there is debate as to which, if any, of these techniques leads to improved clinical outcomes over another and there is a lack of data comparing them. In this review, currently published and distinct techniques of mechanical thrombectomy are described methodically along with illustrations to aid in understanding the subtle differences between the techniques. The perceived benefits of each variation are discussed.
Article
Full-text available
Context Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed.Objective To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion.Design PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998.Setting Fifty-four centers in the United States and Canada.Patients A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan.Intervention Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59).Main Outcome Measures The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality.Results For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06).Conclusion Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days. Figures in this Article Intravenous (IV) tissue-type plasminogen activator (tPA) improves outcomes after acute ischemic stroke but must be given within 3 hours of onset.1 Six randomized trials have failed to show an overall benefit for IV thrombolytic therapy initiated within 6 hours of stroke onset.2- 7 A number of factors have contributed to this failure, but stroke heterogeneity has been cited as a main cause.8- 9 A focused trial of a homogeneous stroke population provides an alternative to the traditional large, randomized clinical trial.9 Intra-arterial (IA) thrombolysis lends itself to such a design in selected patients with acute ischemic stroke.10- 16 The recanalization efficacy and safety of IA recombinant prourokinase (r-proUK) in patients with acute ischemic stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion were demonstrated in the first Prolyse in Acute Cerebral Thromboembolism (PROACT I) trial.17 Prolyse (nasaruplase beta) is a glycosolated 411–amino acid single-chain proenzyme precursor of urokinase (UK) derived from transfected murine SP2/0 hybridoma cells.18 Single-chain r-proUK is activated to 2-chain UK at the thrombus surface by fibrin-associated plasmin.19 The thrombolytic effect of r-proUK is augmented by heparin, possibly through thrombin neutralization or by stimulating tPA release from the endothelium.20- 21 Based on PROACT I, we performed a multicenter, randomized trial to determine the clinical efficacy and safety of IA r-proUK in patients with acute ischemic stroke of less than 6 hours duration caused by MCA occlusion. In PROACT II, we increased the total dose of r-proUK from 6 mg to 9 mg given over 2 hours while using the same low heparin dose as in PROACT I in an attempt to improve recanalization while limiting symptomatic brain hemorrhages.
Article
Full-text available
To evaluate efficacy and clinical benefit of early thrombolytic therapy in intracranial internal carotid artery occlusion. Thirty-two patients (mean age, 56 years) with acute intracranial internal carotid artery occlusion were studied clinically and with CT and angiography before and after thrombolytic therapy with intravenous alteplase (n = 16), superselective intraarterial alteplase (n = 8), and superselective intraarterial urokinase (n = 8). Initial CT showed a large parenchymal hypodensity in 11 (34%) patients, a small hypodensity in 15 (47%) patients, and no hypodensity in 6 (19%) patients. Recanalization after thrombolytic therapy was observed in 4 patients (12.5% in each treatment group). Follow-up CT showed six hemorrhagic infarcts and four parenchymal hematomas unrelated to recanalization, alteplase, or urokinase administration, but commonly associated with intraarterial treatment. Clinical outcome was fatal in 53%, poor in 31%, and moderate or good in 16% of the patients. Outcome was equal in different treatment groups and closely linked to both the quality of leptomeningeal collaterals and the extent of parenchymal hypodensity on the first CT. Because intravenous or intraarterial treatment with alteplase or urokinase fails to recanalize the vascular obstruction, it does not improve the prognosis of intracranial internal carotid artery occlusion over that of the natural course. Improved results may be possible with novel recanalization techniques.
Article
Full-text available
In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Trial found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. In the NINDS Trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a "favorable outcome," defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at 12 months, 95 percent confidence interval, 1.7; 1.2 to 2.3). The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the t-PA group and the placebo group (24 percent vs. 28 percent, P=0.29). There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response. The rate of recurrent stroke at 12 months was similar in the two groups. During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability, than the patients given placebo. These results indicate a sustained benefit of t-PA for such patients.
Article
Background and purpose: To investigate the feasibility and safety of a combined intravenous (IV) and intra-arterial (IA) approach to recanalization in patients with ischemic stroke. Materials and methods: Subjects ages 18 to 80 with an NIH Stroke Scale (NIHSS) > or =10 at baseline had IV recombinant tissue plasminogen activator (rt-PA) started (0.6 mg/kg, 60 mg maximum over 30 minutes) within 3 hours of onset. Additional rt-PA was then administered via microcatheter at the site of the thrombus up to a total dose of 22 mg over 2 hours of infusion or until thrombolysis. Primary comparisons were with similar subsets of placebo and rt-PA-treated subjects from the NINDS rt-PA Stroke Trial. Results: The 80 subjects had a median baseline NIHSS score of 18. The median time to initiation of IV rt-PA was 140 minutes as compared with 108 minutes for placebo and 90 minutes for rt-PA-treated subjects in the NINDS rt-PA Stroke Trial. The 3-month mortality in Interventional Management Study (IMS) subjects (16%) was numerically lower but not statistically different than the mortality of placebo (24%) and rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic intracerebral hemorrhage (6.3%) in IMS subjects was similar to that of rt-PA-treated subjects (6.6%) but higher than the rate in placebo-treated subjects (1.0%, P=0.018) in the NINDS rt-PA Stroke Trial. IMS subjects had a significantly better outcome at 3 months than NINDS placebo-treated subjects for all outcome measures (odds ratios > or =2). Conclusions: A randomized trial of standard IV rt-PA as compared with a combined IV and IA approach is needed.
Article
Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials. We performed a randomized, double-blind trial of intravenous recombinant tissue plasminogen activator (t-PA) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke. METHODS: The trial had two parts. Part 1 (in which 291 patients were enrolled) tested whether t-PA had clinical activity, as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale (NIHSS) or the resolution of the neurologic deficit within 24 hours of the onset of stroke. Part 2 (in which 333 patients were enrolled) used a global test statistic to assess clinical outcome at three months, according to scores on the Barthel index, modified Rankin scale, Glasgow outcome scale, and NIHSS: RESULTS: In part 1, there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the t-PA group at three months for all four outcome measures. In part 2, the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed (global odds ratio for a favorable outcome, 1.7; 95 percent confidence interval, 1.2 to 2.6). As compared with patients given placebo, patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales. Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo (P < 0.001). Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group (P = 0.30). CONCLUSIONS: Despite an increased incidence of symptomatic intracerebral hemorrhage, treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months.
Article
To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) > or =10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.
Article
Thrombolysis may reduce mortality after acute basilar artery (BA) occlusion. We intended to find variables affecting recanalization and clinical outcome in patients with BA occlusion undergoing thrombolytic therapy. We analyzed in retrospect the clinical and angiographic data of a consecutive series of 51 patients treated with intra-arterial urokinase (n = 44; 0.3 to 1.5 mIU) or intravenous or intra-arterial recombinant tissue plasminogen activator (n = 7; 22 to 100 mg). We identified effective variables by multiple logistic regression analyses and univariate tests. Sites of occlusion were the caudal (n = 23), middle (n = 18), and distal (n = 10) segments of the BA. The pathogenesis was embolism in 35 and local atherothrombosis in 16 patients. Collateral circulation was good in 32 patients and poor or absent in 19 patients. Recanalization was achieved in 26 of 51 (51%) patients and was associated with occlusions of embolic etiology (P = .0025). Mortality was 46% (12/26) in the recanalization group and 92% (23/25) in the nonrecanalization group (P = .0004). Other independent variables affecting mortality were length of BA obstruction (P = .0011), age (P = .0008), and collateral state (P = .0454). After follow-up (median, 32 months), 10 of the 16 survivors were only minimally impaired, with a Barthel Index score of 95 or greater; 5 patients were moderately and 1 severely disabled. Recanalization of acute BA occlusion reduces mortality significantly. Length of BA obstruction and state of the collaterals are additional independent variables affecting survival. Young patients with monosegmental embolic occlusion of the BA seem to have the best chance to considerably profit from thrombolysis.