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.
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below....
The response from the Stenting and Aggressive Medical Management for
the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal
investigators (PIs) is greatly appreciated. Healthy debate helps us weed
out the details that are important in these studies and future trial
design. Although the PIs label some of the editorial comments as
"inaccuracies", one could disagree based on the information listed below.
So let's look at the numbers and the facts.
First, they state the SAMMPRIS population was the right population to
test, based on the Warfarin versus Aspirin for Symptomatic Intracranial
Disease (WASID) trial data. However, they base this statement on the
criteria of the degree of stenosis, and some standard, but relatively
artificial epidemiological criteria, not focusing on some other important
clinical criteria. For example, the mean time of enrollment from
qualifying event to enrollment was 17 days in the WASID trial and 7 days
in the SAMMPRIS trial, so these are not exactly the same patient
populations. The patients who were stented in SAMMPRIS within 7 days of
their qualifying event did remarkably worse than the patients stented
after day 7, indicating that either these patients had unstable plaque or
some other factor that increased their risk for complications when treated
early. The Wingspan safety trial that led to FDA approval of the Wingspan
stent did NOT include patients who had stroke less than 7 days, so to
stent patients at less than 7 days from the event was another variable
introduced by the SAMMPRIS trial design that was not a part of the
original Food and Drug Administration (FDA) approval of the stent.
Second, they state that the Wingspan stent was not used off-label.
This is not exactly true. The Investigational Device Exemption (IDE) use
of the Wingspan stent in the SAMMPRIS trial was used for expanded
indications compared to the Humanitarian Device Exemption (HDE) FDA
approval. In fact, this was exactly one of the reasons that an IDE
approval was necessary for the trial. Interestingly, if one analyzes the
presenting symptoms, time to treatment, medical failure, and other
factors, only 8% of the patients enrolled in SAMMPRIS would have qualified
for the original Wingspan safety study upon which the FDA granted approval
(FDA Panel Review, March 2012, Baltimore, MD). Therefore, practices such
as treating patients before day 7 post-event, allowing TIA versus stroke
only as an entry criteria, and allowing patients who had not failed
medical therapy into the trial, were markedly expanded indications for the
stent in this trial. For this reason, one could argue that this trial was
not designed for stenting to succeed. Typically, every device trial is
initially designed for the on-label indication, and only later are there
considerations for expanded indications. This was not the paradigm used
in SAMMPRIS. In the subgroup of the 8% of patients in SAMMPRIS that
actually would have qualified for the original Wingspan safety trial,
there was no statistical difference in clinical outcomes between the
stenting and the medical therapy groups.
Third, the argument that even the subgroup of patients who previously
failed anti-platelet therapy did worse with stenting than medical therapy
is easily predictable, if you look how stented patient were managed in the
study. Many major centers test patients for anti-platelet therapy
resistance prior to stent placement, since there is a documented 15%
relative clopidogrel resistance in the population and 10% aspirin
resistance. Patients who are resistant to anti-platelet therapy are more
likely to have a thromboembolic event with a fresh stent placement, as a
nidus for platelet aggregation than someone with a chronic atherosclerotic
stenosis. The SAMMPRIS trial failed to account for possible anti-platelet
therapy resistance as many coronary stenting trials current address. In
fact, it was a protocol violation in SAMMPRIS even to measure the anti-
platelet therapy resistance.
Finally, the argument that interventionalist experience did not play
a role in the results is very short-sighted and is based on poorly
stratified data. It would be difficult to believe that anyone would argue
that less experienced stenters could have equivalent clinical results than
more experienced stenters. The average number of Wingspan stents placed
by interventionalists to qualify as a stenter in the study was 10 Wingspan
stents. This low number, as a distinction between low and high volume
stenters, would not be acceptable in any current stenting trial:
coronary, carotid, peripheral, etc. So technically, both "low volume" and
"high volume" groups analyzed by the PIs were low volume users.
The goals for the future should be to focus our attention on defining
which population will benefit most with revascularization, what is the
best timing for the procedure, and what medical therapy regimen is best
for patients with newly placed intracranial stents, which may not be the
same as the best therapy for those without stents. SAMMPRIS gives a
significant amount of information, but it is a starting point, not an end
to this therapy.
Conflict of Interest:
Dr. Alexander was an investigator in the SAMMPRIS clinical trial. He is a device proctor and consultant for Styker Neurovascular which manufactures the Wingspan stent.
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
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.
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.
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
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
As the first author (and the senior author) I am wholly responsible
for any errors in the paper, including errors of attribution. I apologize
first to our readers, and second to Dr. Altes, whose contributions are
significant and are of continuing value.
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 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.
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...
The response from the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial principal investigators (PIs) is greatly appreciated. Healthy debate helps us weed out the details that are important in these studies and future trial design. Although the PIs label some of the editorial comments as "inaccuracies", one could disagree based on the information listed below....
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...
Dear Author & Editor
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 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...
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...
To the Editor:
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...
As the first author (and the senior author) I am wholly responsible for any errors in the paper, including errors of attribution. I apologize first to our readers, and second to Dr. Altes, whose contributions are significant and are of continuing value.
Charles Kerber M.D.
Conflict of Interest:
None declared
Dear Editor,
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...
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...
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