We greatly appreciate the input by Dr. Chandra and colleagues. Our
paper was a highly focused, empiric exercise to determine, based on
morphology alone, the potential for endoluminal implants for treatment of
aneurysms. There are myriad additional factors that, without question,
will affect the appropriateness of such devices for a given aneurysm,
including aneurysm rupture status, patient condition, age, tolerance of...
We greatly appreciate the input by Dr. Chandra and colleagues. Our
paper was a highly focused, empiric exercise to determine, based on
morphology alone, the potential for endoluminal implants for treatment of
aneurysms. There are myriad additional factors that, without question,
will affect the appropriateness of such devices for a given aneurysm,
including aneurysm rupture status, patient condition, age, tolerance of
antiplatelet agents, vascular access, and others that will become apparent
as these devices gain widespread use.
We welcome the comments by Dr. Chandra and colleagues regarding the
FDA approval status of the device. Of course, the work performed for
that paper was done long before the device was even submitted for FDA
approval, and represents a "thought experiment" rather than a clinical
trial. We, as they, assume that physicians are capable of reading the
package insert to determine the type of aneurysm for which the device was
specifically approved. We also assume that, as with many or most devices
approved under the Premarket Approval process, actual usage will extend
far beyond the "on-label" indication. We genuinely hope that such "off-
label" usage will be done in the setting of prospective, controlled
studies if at all possible, such studies that in the future might lead to
or away from FDA approval for expanded indications.
I read with interest the paper by Kerber, et al. entitled "1-Hexyl n-
cyanoacrylate compound (Neucrylate_AN), a new berry aneurysm treatment.
II. Rabbit implant studies: technique and histology." (1) As suggested by
the title, the paper focuses on the preclinical evaluation of a new device
in a rabbit model. However, the references and discussion are misleading
and may well confuse researchers inten...
I read with interest the paper by Kerber, et al. entitled "1-Hexyl n-
cyanoacrylate compound (Neucrylate_AN), a new berry aneurysm treatment.
II. Rabbit implant studies: technique and histology." (1) As suggested by
the title, the paper focuses on the preclinical evaluation of a new device
in a rabbit model. However, the references and discussion are misleading
and may well confuse researchers intending to reproduce the authors'
experiments.
The model used in the paper by Kerber, et al. is the widely-applied,
elastase-induced aneurysm model originally published by Altes, et al (2).
This simple model uses intraluminal elastase incubation to covert a
preexisting arterial lumen, the right common carotid artery, into an
aneurysmal stump. However, the methods of the paper by Kerber, et al. (1)
reference a completely distinct and different model published by
Miscolizik, et al (3). That latter model used extraluminal elastase
applied to arterial bifurcations, with resultant aneurysms forming acutely
but no chronic experiments described. Thus, readers of the paper by
Kerber, et al. should be advised that the periadventitial model of
Miskolczi, et al. was not, in fact utilized.
Further, the authors go on to note in their discussion that "In 1998,
Miskolczi, et al. developed a rabbit aneurysm model that provided a close
to ideal testing milieu for endovascular, particularly intra-arterial,
devices." In fact, I am unable to find a single study that has used that
the model of Miskolczi, et al. to test any device. Finally, Kerber, et
al. write that "An extensive literature has accumulated since Miskolczi's
original paper- a literature describing device behaviors and a wall
response to the introduction of foreign devices." The "extensive
literature" again has nothing to do with the paper by Miscolczi, but
rather describes work done using the elastase-induced model of Altes, et
al.
Clarity and precision are essential aspects of all medical
literature, both clinical and preclinical. Accurate references to animal
models will speed development of devices for the benefit of patients
suffering from intracranial aneurysms.
References
1. Kerber CW, Pakbaz RS, Hasteh F, et al. 1-Hexyl n-cyanoacrylate
compound (Neucrylate™ AN), a new berry aneurysm treatment. II.
Rabbit implant studies: technique and histology. J Neurointerv Surg. 2012
Jan 1;4(1):50-7. Epub 2011 Jun 8.
2. Altes TA, Cloft HJ, Short JG, et al.. 1999 ARRS Executive
Council Award. Creation of saccular aneurysms in the rabbit: a model
suitable for testing endovascular devices. American Roentgen Ray Society.
AJR Am J Roentgenol. 2000 Feb;174(2):349-54.
3. Miskolczi L, Guterman LR, Flaherty JD, et al. Saccular aneurysm
induction by elastase digestion of the arterial wall: a new animal model.
Neurosurgery. 1998 Sep;43(3):595-600; discussion 600-1.
Conflict of Interest:
Dr. Kallmes receives research support from MicroVention, Micrus, Penumbra, NFocus, Sequent, and eV3.
We would like to add our strong support to the recent editorial by
Fiorella, et al. Dr. Fiorella and his colleagues should be congratulated
for pointing out the giant elephant in the room. The government, insurers
and patients are increasingly demanding more quality, safety and value
from the healthcare dollar and, like it or not, we can no longer ignore
their pleas. Dr. Fiorella has eloquently shown us with widely ava...
We would like to add our strong support to the recent editorial by
Fiorella, et al. Dr. Fiorella and his colleagues should be congratulated
for pointing out the giant elephant in the room. The government, insurers
and patients are increasingly demanding more quality, safety and value
from the healthcare dollar and, like it or not, we can no longer ignore
their pleas. Dr. Fiorella has eloquently shown us with widely available
data that our profession now has more than enough manpower to handle the
labor demands extending into the foreseeable future. The current trend of
overproducing neurointerventional fellows has already led to decreased
quality and safety and is a profound misallocation of scarce medical
resources. These issues are further compounded by the current lack of a
standardized training curriculum and certifying examination.
One other factor that was not mentioned in the editorial is the
inevitable replacement of the fee for service payment model with bundled
payments or some similar type of payment distribution. It is not a
question of if this change will occur, but rather when it will occur.
Because the procedures we perform are very expensive, our specialty will
be under tremendous scrutiny by the accountable care organizations or
other entities that are tasked with managing and allocating the funds for
these bundled payments. Simply put, this paradigm shift in healthcare
financing will demand that neurointerventionalists intervene only in those
situations that are proven effective and provide value. In a world of
bundled payments, the focus will absolutely be on conservative medical
management rather than complex and expensive interventions. As painful as
it may seem to those of us who perform these procedures, it is inevitable.
We believe this will contribute to declining neurointerventional volumes
in the near future and is why we should halt all neurointerventional
fellowship training until there is adequate volume to maintain expertise
among current practitioners.
Unfortunately, we might be too late to stop this runaway train.
Given the number of fellows currently being trained and the relatively low
rate of retirement from our specialty at this time, we will experience a
glut of neurointerventionalists in the next few years. Because there is
no consistent scrutiny of quality in the neurointerventional fellowships,
there are "puppy mill" fellowships popping up all over the country. These
fellowships do not provide adequate procedure complexity, volume or
oversight to produce even a marginally competent neurointerventionalist.
Sadly, we have seen the recent intrusion of this type of subpar training
program into our medical community with as many as six fellows being
trained simultaneously in community, suburban, nonacademic hospital
facilities. Those of us who practice in the larger, academic, tertiary
referral hospitals are now seeing the unfortunate consequences imposed
upon the patients. The disasters range from procedures that clearly
should have never been attempted, even by experienced operators, to
procedures that are declined due to being "technically difficult" despite
really being rather straightforward and clinically warranted.
Obviously, we are just as passionate about this crisis as Dr.
Fiorella and his long list of distinguished coauthors. While it might be
too late to avert our current crisis, the impact could be dampened if all
future fellows that have not yet started their programs and those that are
considering our profession were to strongly consider these circumstances
and perhaps choose a different subspecialty.
The paper by Dashti et al. (1) describes 13 patients who received
mechanical thrombectomy with the AngioJet device as first line treatment
for cerebral venous thrombosis (CVT). Mechanical thrombectomy is a
promising alternative to endovascular thrombolysis with thrombolytic
drugs. Hemorrhagic infarcts are common among CVT patients and it is
plausible - although unproven - that mechanical thrombec...
The paper by Dashti et al. (1) describes 13 patients who received
mechanical thrombectomy with the AngioJet device as first line treatment
for cerebral venous thrombosis (CVT). Mechanical thrombectomy is a
promising alternative to endovascular thrombolysis with thrombolytic
drugs. Hemorrhagic infarcts are common among CVT patients and it is
plausible - although unproven - that mechanical thrombectomy gives less
hemorrhagic complications.
There are however some issues that render the authors' suggestion to
use mechanical thrombectomy as a first line treatment for CVT untenable.
First, the paper gives insufficient information about the baseline
condition of the patients, especially the presence of intracranial
hemorrhages before the procedure. The Glasgow Coma Scale was optimal in 7
patients. In the absence of additional risk factors for a poor prognosis -
not mentioned by the authors - we would not treat these patients with
endovascular therapy. Second, follow-up is incomplete, and there is no
control group in the study. Without a control group it is impossible to
conclude that endovascular treatment is better than standard treatment.
The prognosis of CVT after heparin treatment is usually good. In the
'International study on cerebral vein and dural sinus thrombosis' (ISCVT),
a prospective study of 624 patients, mortality at discharge was 4% with
non-invasive anticoagulant treatment (2). This is better than the 15% peri
-operative mortality (2 out of 13) reported by Dashti et al.
We therefore disagree with the suggestion that mechanical
thrombectomy should be considered as first line treatment for CVT. In
patients without risk factors for a poor prognosis, anticoagulant
treatment according to international guidelines (3,4) is usually
effective. Patients with one or more risk factors may benefit from
endovascular treatment, but there are no appropriately controlled studies.
Therefore, we recently launched the TO-ACT study (Thrombolysis Or
Anticoagulation for Cerebral venous Thrombosis), an international
randomized trial (www.clinicaltrials.gov; NCT01204333). Patients are
eligible if they have severe CVT, as defined by the risk factors:
intracranial hemorrhage, coma, mental status disorder or thrombosis of the
deep venous system. The type of endovascular treatment is to be decided by
the local investigator and may be pharmacological, mechanical, or a
combination. A sensitivity analysis of the type of endovascular
thrombolysis is planned. More information about the trial is available at
www.to-act-trial.org.
JM Coutinho, R van den Berg, SM Zuurbier, CB Majoie and J Stam
Academic Medical Center, Amsterdam, the Netherlands
j.coutinho@amc.uva.nl
References
1. Dashti SR, Hu YC, Yao T, Fiorella D, Mitha AP, Albuquerque FC,
McDougall CG. Mechanical thrombectomy as first-line treatment for venous
sinus thrombosis: technical considerations and preliminary results using
the AngioJet device. J Neurointerv Surg. 2011 Dec 5. [Epub ahead of print]
2. Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F.
Prognosis of
cerebral vein and dural sinus thrombosis: results of the International
Study on
Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke. 2004;35:664-70.
3. Einhaupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli
I, Masuhr F; European Federation of Neurological Societies. EFNS guideline
on the treatment of cerebral venous and sinus thrombosis in adult
patients. Eur J Neurol. 2010 Oct;17(10):1229-35.
4. Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD,
Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart
Association Stroke Council and the Council on Epidemiology and Prevention.
Diagnosis and management of cerebral venous thrombosis: a statement for
healthcare professionals from the American Heart Association/American
Stroke Association. Stroke. 2011 Apr;42(4):1158-92
We thank Coutinho and colleagues for their comments on our
manuscript. They state that the 4% mortality associated with noninvasive
anticoagulant treatment in the International Study on Cerebral Vein and
Dural Sinus Thrombosis (ISCVT) is superior to our observed mortality rate
of 15% (2 of 13 patients). The ISCVT is a large prospective trial, which
is detailed in the Discussion of our article. A direct comparison of
m...
We thank Coutinho and colleagues for their comments on our
manuscript. They state that the 4% mortality associated with noninvasive
anticoagulant treatment in the International Study on Cerebral Vein and
Dural Sinus Thrombosis (ISCVT) is superior to our observed mortality rate
of 15% (2 of 13 patients). The ISCVT is a large prospective trial, which
is detailed in the Discussion of our article. A direct comparison of
mortality rates between ISCVT and our small case series is not meaningful.
In our series the 15% mortality rate was related to the damage that was
already done by venous sinus thrombosis. These patients were already
neurologically devastated before our intervention—their deaths were not
a result of the procedure. It is even possible that outcomes would have
been better had we intervened in those patients sooner. We have been
involved in several cases where patients were managed with anticoagulation
initially for some time but continued to worsen. By the time mechanical
thrombectomy was brought to the table, they were already devastated.
Coutinho and colleagues state that in the absence of additional risk
factors for a poor prognosis, they would not treat any patients with
endovascular therapy. However, they do not consider the problems
associated with long-term refractory headaches often experienced by sinus
thrombosis patients. In our series all 6 patients who presented primarily
with severe headaches experienced complete and immediate resolution of
their headaches after mechanical thrombectomy.
Coutinho et al. also point out that there was no control group in our
series and that follow up was incomplete. These issues of course reflect
the retrospective nature of this case series; it was not a randomized
controlled trial. The key point of our report is that endovascular
therapy for venous sinus thrombosis can be performed with minimal risk in
experienced hands. Mechanical intervention markedly reduces the volume of
thrombus and quickly restores flow. Once flow is established, the residual
thrombus responds more completely and more quickly to systemic
anticoagulation. We believe this approach greatly reduces the duration and
severity of symptoms and can shorten hospital stays and the required
convalescence period.
Shervin R. Dashti, M.D.
Louisville, Kentucky
Cameron G. McDougall, M.D.
Phoenix, Arizona
I write to congratulate the authors on a fine basic review of spinal
cord vasculature and related imaging modalities, but also to point out
that as time goes by, the older literature may fall by the wayside,
largely forgotten. Ordinarily I try not to act like a dinosaur and point
such things out, but the authors do mention (on page 69) in reviewing the
vascular supply of the cervical spinal cord, that "according to
"Dji...
I write to congratulate the authors on a fine basic review of spinal
cord vasculature and related imaging modalities, but also to point out
that as time goes by, the older literature may fall by the wayside,
largely forgotten. Ordinarily I try not to act like a dinosaur and point
such things out, but the authors do mention (on page 69) in reviewing the
vascular supply of the cervical spinal cord, that "according to
"Djindjan", other small contributors may arise from the costocervical
trunk....". Not only is the name misspelled (I imagine this could have
been an error in editing at the journal), but Dr. Djindjian is quoted and
yet there is no cited reference to his pioneering work anywhere in the
manuscript. I assume that one of the authors is familiar with his work,
and wanted to credit him in this way and that is commendable.
We who work and have worked on patients with neurovascular disease of
the cord owe much to the work of Rene Djindjian, formerly professor and
chief of the Department of Neuroradiology at l'Hopital Lariboisiere in
Paris. He took the relatively new (at the time) technique of selective
angiography, and applied it to the spinal cord and spinal cord disease.
There are ample opportunities for citations: his countless peer reviewed
papers, as well as his (now sadly long out of print) classic text,
L'Angiographie De La Moelle Epiniere (Angiography of the Spinal Cord),
authored by Djindjian (as well as co-authors including Hurth and Houdart)
with a preface by Guy Lazorthes (formerly Chief of Neurosurgery, and Dean
of the University of Medicine and Pharmacy of Toulouse), translated into
English by Irvin I. Kricheff (New York), and published in 1970 (Masson
& Cie, Paris and University Park Press, Baltimore, 482pp).
I do not mean to say that we must be familiar with everything from
the past that informs our current practice, but it is important to not
forget those who were so critical in advancing the dynamic field that
benefits so many of our patients today. Again, I credit the authors for
remembering this. I write primarily for the sake of those who may read
this paper who may not know of Djindjian's work and may learn from it more
directly. Anyone currently working in the field of Neurointerventional
Surgery should make an effort to find a copy of this text, and learn from
a master.
I appreciate that case reports are extremely important in
establishing the potential viability of interventions. However, it is an
overstatement to conclude that a single case report demonstrates the
"safety" of the given approach.
What the case report does indicate is that the technique is feasible
and that it can be performed safely in this one case and agreeably merits
fur...
I appreciate that case reports are extremely important in
establishing the potential viability of interventions. However, it is an
overstatement to conclude that a single case report demonstrates the
"safety" of the given approach.
What the case report does indicate is that the technique is feasible
and that it can be performed safely in this one case and agreeably merits
further work to establish the overall safety.
As the Principal Investigators for the Stenting and Aggressive
Medical Management for the Prevention of Recurrent Ischemic Stroke
(SAMMPRIS) trial, we are compelled to address a few inaccuracies regarding
this study in the recent editorial by Dr. Alexander.
The first point is the patient population. The SAMMPRIS population
was the right patient population to test. We had very good data from the
Warfarin vers...
As the Principal Investigators for the Stenting and Aggressive
Medical Management for the Prevention of Recurrent Ischemic Stroke
(SAMMPRIS) trial, we are compelled to address a few inaccuracies regarding
this study in the recent editorial by Dr. Alexander.
The first point is the patient population. The SAMMPRIS population
was the right patient population to test. We had very good data from the
Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial
that patients with recently symptomatic severe stenosis were at the
highest risk for recurrent stroke 1. This high risk population offered
the best chance for showing a benefit with revascularization. Much of
the criticism in the editorial has the benefit of hindsight. The
hemodynamic versus embolic mechanisms for stroke may be important in
defining groups that benefit from angioplasty in the future 2. This
distinction does not matter for extracranial carotid disease, as
revascularization works regardless of mechanism. It may matter for
intracranial atherosclerotic disease. Finally, in designing a trial,
there are always groups of patients that will not be included, such as the
high risk unstable patients described in the editorial. Our data does not
address treatment of these patients one way or the other and that should
not be a criticism of the trial.
Second, the Wingspan stent was not used off-label in the trial. It
is true that we used the stent under a Food and Drug Administration
Investigational Device Exemption that was not the same as the Humanitarian
Device Exemption (HDE) for the stent. This does not make the SAMMPRIS
results "dubious". SAMMPRIS conclusively showed that angioplasty and
stenting for the high risk WASID population was worse than aggressive
medical management. Moreover, a subgroup analysis in patients who had
failed antithrombotic therapy at the time of their qualifying event for
SAMMPRIS (i.e., those patients that met the HDE criteria) also showed that
angioplasty and stenting was worse than aggressive medical management in
these patients (Lutsep, et al., 2012 International Stroke Conference, Los
Angeles, CA).
Finally, there was never a policy that all 20 cases of angioplasty
and stenting submitted for credentialing had to be with the Wingspan
device, as stated by Dr. Alexander. We required documentation of 20
consecutive intracranial angioplasty and/or stenting cases and accepted
experience with similar devices 3. These cases and their outcomes were
carefully reviewed by a credentialing committee composed of experienced
neuro interventionists. The fact that interventionists with the least
experience with Wingspan had similar event rates as those with the highest
experience indicates that this system identified a very capable group of
neurointerventionists (Derdeyn, et al., 2012 International Stroke
Conference, Los Angeles, CA). In at least one of the carotid stenting
trials mentioned by Dr. Alexander, some interventionists were allowed to
participate without the requisite experience as long as they were
proctored during the procedure 4. Others were allowed in with as few as
five total carotid angioplasty and stenting cases (with any device). This
was not permitted in SAMMPRIS.
We agree wholeheartedly that we still have much to learn about this
disease and its treatment.
Sincerely,
References:
1. Kasner SE, Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ,
Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Benesch CG, Sila CA,
Jovin TG, Romano JG, Cloft HJ. Predictors of ischemic stroke in the
territory of a symptomatic intracranial arterial stenosis. Circulation.
2006;113:555-563
2. Derdeyn CP. Mechanisms of ischemic stroke secondary to large artery
atherosclerotic disease. Neuroimaging Clin N Am. 2007;17:303-311, vii-viii
3. Chimowitz MI, Lynn MJ, Turan TN, Fiorella D, Lane BF, Janis S, Derdeyn
CP. Design of the stenting and aggressive medical management for
preventing recurrent stroke in intracranial stenosis trial. J Stroke
Cerebrovasc Dis. 2011;20:357-368
4. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP,
Larrue V, Lievre M, Leys D, Bonneville JF, Watelet J, Pruvo JP, Albucher
JF, Viguier A, Piquet P, Garnier P, Viader F, Touze E, Giroud M, Hosseini
H, Pillet JC, Favrole P, Neau JP, Ducrocq X. Endarterectomy versus
stenting in patients with symptomatic severe carotid stenosis. N Engl J
Med. 2006;355:1660-1671
We salute Dr. Ghobrial and colleagues for their important
contribution regarding the endovascular management of elderly ischemic
stroke patients.1 Although this topic is relatively new to the literature,
it is of critical importance to the field of intra-arterial therapy (IAT)
given the increasing use of catheter-based stroke therapies2 and the
expanding population of elderly Americans, who are at the highest risk for
isc...
We salute Dr. Ghobrial and colleagues for their important
contribution regarding the endovascular management of elderly ischemic
stroke patients.1 Although this topic is relatively new to the literature,
it is of critical importance to the field of intra-arterial therapy (IAT)
given the increasing use of catheter-based stroke therapies2 and the
expanding population of elderly Americans, who are at the highest risk for
ischemic stroke.
The authors conducted an extensive, retrospective single-center study
using chart review that identified elderly patients (aged ?75years) that
underwent IAT between 2006-2012. The minimum NIHSS score used in this
analysis was 8, and patients were selected using NCCT between 2006-2009,
and from 2009 onwards, additional CTA and CTP studies were performed. The
recanalization rate (TIMI 2-3) was 65% with symptomatic intracranial
hemorrhage occurring in 6%. All-cause mortality was 22% with two deaths
from intra-operative vessel rupture. The average discharge mRS score was
3.9 and overall 33% of elderly patients achieved favorable outcome (mRS 0-
3). The authors have concluded that "multimodal endovascular management of
acute ischemic stroke in patients over 75 years old is safe and
effective".
In our view, these results warrant a more cautious conclusion than
the one advocated in in the manuscript. The natural question is "safe and
effective" compared to what? Is it as safe and effective as treatment in a
younger cohort? To answer this question, a comparison with a concurrent
population of younger patients treated with IAT at the same center would
be necessary, although this was not performed. Is it as safe and effective
as IV tPA or best medical management? Such control groups were not
studied. The reader is left to compare these results with those of other
centers. However, as the authors state in their discussion, comparing
treatment outcomes between centers is complicated by varying patient
selection criteria and treatment algorithms. Similarly, the definitions of
outcomes vary significantly between the studies and ultimately prevent
between-center comparisons.
In the growing body of literature on IAT and post-stroke outcomes in
the elderly, there are no randomized controlled data evaluating IAT
efficacy versus IV tPA or best medical management. Most papers, including
a recent retrospective study from our group, report treatment results
between elderly and non-elderly cohorts treated concurrently in the same
center.3-7 These papers suggest that there are similar rates of
revascularization and significant reperfusion hemorrhage between the two
age groups. This last point supports that IAT is safe in older patients.
However, mortality is also significantly increased in the elderly cohort.
Most interestingly, achieving functional independence (mRS 0-2) at 90
-days post-stroke by the elderly ranges greatly from 0 to ~45%. In our
paper, we suggest that this may be related in part to differences in
baseline health and disability status among the older patients. This is
supported by the prior reports of co-morbidities influencing IAT outcomes
in the Merci and Multi-Merci trials.8 Furthermore, a separate analysis
from our institution demonstrated that pre-stroke dementia is an
independent predictor of poor outcomes in the elderly.9 On the other hand,
high variability in the post-stroke outcomes in the elderly allows for a
possibility that a certain subset of elderly patients may benefit from
this treatment; however, more data are needed to clarify this question.
Until prospective, systematically collected data are available,
though, what approach should we advocate for in the elderly patients who
are otherwise eligible for acute stroke intervention? We previously
reported on a institutional protocol developed and implemented by our
multidisciplinary Acute Stroke Service (Stroke Neurology and
NeuroInterventional services) that aims to stratify acute stroke patients
into groups that are most likely, uncertain or unlikely to benefit from
IAT based on established predictors of outcome after catheter-based
therapy.10 Future modifications to this algorithm including the emerging
data on age and dementia will be incorporated and studied prospectively
and in a systematic way in order assess on the effects of novel
determinants of post-stroke outcomes in IAT patients.
Because outcomes data are conflicting and because some elderly
patients may regain independence after IAT, such patients should not be
excluded from consideration for treatment. Furthermore, our existing
patient-selection algorithm may change after greater clinical experience
with stentrievers, as the greater degree and speed of reperfusion afforded
by this technology may particularly benefit the elderly population, who
may have reduced neuronal reserve compared to younger patients. However
this is a theoretical consideration at this time, pending accumulation of
further experience and data.
Overall, based on the accumulated evidence, it is reasonable to
conclude that IAT is safe in the elderly. However, any conclusion
regarding its effectiveness remains premature and will require further
study.
References
1. Ghobrial GM, Chalouhi N, Rivers L, et al. Multimodal endovascular
management of acute ischemic stroke in patients over 75 years old is safe
and effective. J Neurointerv Surg. 2012.
2. Hirsch JA, Yoo AJ, Nogueira RG, et al. Case volumes of intra-
arterial and intravenous treatment of ischemic stroke in the USA. J
Neurointerv Surg. 2009;1(1):27-31.
3. Chandra RV, Leslie-Mazwi TM, Oh DC, et al. Elderly Patients Are at
Higher Risk for Poor Outcomes After Intra-Arterial Therapy. Stroke. 2012.
4. Mono M-L, Romagna L, Jung S, et al. Intra-Arterial Thrombolysis
for Acute Ischemic Stroke in Octogenarians. Cerebrovasc Dis.
2012;33(2):116-122.
5. Qureshi AI, Suri MFK, Georgiadis AL, Vazquez G, Janjua NA. Intra-
Arterial Recanalization Techniques for Patients 80 Years or Older with
Acute Ischemic Stroke: Pooled Analysis from 4 Prospective Studies. AJNR Am
J Neuroradiol. 2009;30(6):1184-1189.
6. Loh Y, Kim D, Shi ZS, et al. Higher Rates of Mortality but Not
Morbidity Follow Intracranial Mechanical Thrombectomy in the Elderly. AJNR
Am J Neuroradiol. 2010;31(7):1181-1185.
7. Kim D, Ford GA, Kidwell CS, et al. Intra-arterial thrombolysis for
acute stroke in patients 80 and older: a comparison of results in patients
younger than 80 years. AJNR Am J Neuroradiol. 2007;28(1):159-163.
8. Flint AC, Duckwiler GR, Budzik RF, Liebeskind DS, Smith WS, for
the MERCI and Multi MERCI Writing Committee. Mechanical Thrombectomy of
Intracranial Internal Carotid Occlusion: Pooled Results of the MERCI and
Multi MERCI Part I Trials. Stroke. 2007;38(4):1274-1280.
9. Busl KM, Nogueira RG, Yoo AJ, Hirsch JA, Schwamm LH, Rost NS.
Prestroke Dementia is Associated with Poor Outcomes after Reperfusion
Therapy among Elderly Stroke Patients. J Stroke Cerebrovasc Dis. 2011.
10. Rost NS, Smith EE, Nogueira RG, et al. Implementation of a
patient selection protocol for intra-arterial therapy increases treatment
rates in patients with acute ischemic stroke. J Neurointerv Surg. 2012.
We would like to thank Dr Hirsch and colleagues from Massachusetts
General Hospital for their insightful comment on our paper.1 The authors
advocate a more cautious conclusion regarding the efficacy of endovascular
stroke intervention in the elderly since a control group of younger
patients is lacking in our study. Although comparison to a younger group
of patients is interesting, such data can hardly be used for drawing...
We would like to thank Dr Hirsch and colleagues from Massachusetts
General Hospital for their insightful comment on our paper.1 The authors
advocate a more cautious conclusion regarding the efficacy of endovascular
stroke intervention in the elderly since a control group of younger
patients is lacking in our study. Although comparison to a younger group
of patients is interesting, such data can hardly be used for drawing
definitive conclusions regarding the efficacy of endovascular therapy. A
clinical comparison between young and older patients is unfortunately not
possible due to tremendous differences between the two study populations,
such as pre-existing medical comorbidities and dementia. Randomized
controlled studies comparing patient outcomes with intra-arterial therapy
versus intravenous thrombolysis or best medical management will be needed
to provide definitive information on the best therapeutic approach in this
patient population.
In patients with NIHSS of 8 or above who have failed or were not
eligible for intravenous thrombolysis, such as in our study population,
medical therapy is unfortunately limited to supportive management. Most of
these patients are destined to end of life care or are neurologically
devastated from their stroke. In an era of FDA-approved intra-arterial
thrombolysis, there is an ethical dilemma in randomizing patients that
meet criteria to such life-saving interventions to medical therapies,
regardless of their age group. It is therefore extremely challenging to
obtain level-one evidence data in the elderly or any other age population
comparing medical and endovascular stroke therapies.
Timely recanalization in acute ischemic stroke improves patient
outcomes.2-4 Arterial recanalization can be achieved by intravenous or
intraarterial means. Evidence suggests that treatment benefit with
intravenous tissue plasminogen activator (IV-tPA) extends to patients
older than 80 years.5 It is therefore plausible that intra-arterial
thrombolysis could confer a similar benefit in elderly patients. In our
study, almost a third of elderly patients achieved favorable outcomes with
intraarterial thrombolysis, and similar rates were also reported by other
investigators.6-7 In our opinion, such rates can be regarded as
satisfactory considering the compromised collateral circulation, the
reduced neuronal reserve, as well as the high frequency of pre-stroke
comorbid conditions in this age group. However, we agree with Dr Hirsch
and colleagues that this would require further confirmation by prospective
controlled data.
In a recently published study by Chandra and colleagues8 from
Massachusetts General Hospital, 49 elderly and 130 nonelderly patients
treated between 2005 and 2010 were rigorously compared with respect to
angiographic reperfusion, rate of parenchymal hematoma, and 90-day
clinical outcome. The authors report comparable rates of reperfusion and
hemorrhage between the two groups but favorable outcomes in only 2% of
elderly patients and conclude that recanalization in this group "may be
futile". In our view, these results warrant a more cautious conclusion
than the one advocated in their report not only because comparison to a
control group treated with medical therapy is lacking but also for the
following reasons. 1) Nearly 33% of elderly patients in their study were
disabled at baseline (mRS score 2 or greater), which makes the prospect of
a favorable outcome nearly impossible in as many as one-third of their
cohort. 2) Medical care was withdrawn in 55% of elderly patients, which
obviously complicates any assessment of outcome. 3) CT perfusion data was
not used to select patients for acute stroke intervention, which could
possibly suggest that some patients with little or no salvageable brain
tissue may have undergone endovascular treatment. In fact, CT perfusion
can optimize patient selection for endovascular recanalization based on an
individual's physiological parameters rather than an arbitrary time frame
and may be of greater value in this specific population by helping
identify "the subset of elderly patients who may benefit" from treatment.9
-11
Finally, we agree with Dr Hirsch and colleagues that endovascular
stroke intervention in elderly patients is safe. Although the question of
its efficacy requires more investigation, we believe that elderly patients
should not be excluded from consideration for treatment especially if
perfusion studies indicate adequate penumbra. The significance of proper
patient selection for endovascular recanalization cannot be overstressed.
References
1.Ghobrial GM, Chalouhi N, Rivers L, et al. Multimodal endovascular
management of acute ischemic stroke in patients over 75 years old is safe
and effective. J Neurointerv Surg. Jul 11 2012.
2.Meyers PM, Schumacher HC, Connolly ES, Jr., Heyer EJ, Gray WA,
Higashida RT. Current status of endovascular stroke treatment.
Circulation. Jun 7 2011;123(22):2591-2601.
3.Tissue plasminogen activator for acute ischemic stroke. The
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study
Group. N Engl J Med. Dec 14 1995;333(24):1581-1587.
4.Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3
to 4.5 hours after acute ischemic stroke. N Engl J Med. Sep 25
2008;359(13):1317-1329.
5.Mishra NK, Diener HC, Lyden PD, Bluhmki E, Lees KR. Influence of
age on outcome from thrombolysis in acute stroke: a controlled comparison
in patients from the Virtual International Stroke Trials Archive (VISTA).
Stroke. Dec 2010;41(12):2840-2848.
6.Loh Y, Kim D, Shi ZS, et al. Higher rates of mortality but not
morbidity follow intracranial mechanical thrombectomy in the elderly. AJNR
Am J Neuroradiol. Aug 2010;31(7):1181-1185.
7.Kim D, Ford GA, Kidwell CS, et al. Intra-arterial thrombolysis for
acute stroke in patients 80 and older: a comparison of results in patients
younger than 80 years. AJNR Am J Neuroradiol. Jan 2007;28(1):159-163.
8.Chandra RV, Leslie-Mazwi TM, Oh DC, et al. Elderly Patients Are at
Higher Risk for Poor Outcomes After Intra-Arterial Therapy. Stroke. Jun 28
2012.
9.Abou-Chebl A. Endovascular treatment of acute ischemic stroke may
be safely performed with no time window limit in appropriately selected
patients. Stroke. Sep 2010;41(9):1996-2000.
10.Jovin TG, Liebeskind DS, Gupta R, et al. Imaging-based
endovascular therapy for acute ischemic stroke due to proximal
intracranial anterior circulation occlusion treated beyond 8 hours from
time last seen well: retrospective multicenter analysis of 237 consecutive
patients. Stroke. Aug 2011;42(8):2206-2211.
11.Natarajan SK, Snyder KV, Siddiqui AH, Ionita CC, Hopkins LN, Levy
EI. Safety and effectiveness of endovascular therapy after 8 hours of
acute ischemic stroke onset and wake-up strokes. Stroke. Oct
2009;40(10):3269-3274.
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