Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,365 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label cryptogenic stroke. Show all posts
Showing posts with label cryptogenic stroke. Show all posts
Evidence exists supporting percutaneous patent foramen ovale
(PFO) closure and medical therapy versus medical therapy alone in
selected patients with cryptogenic stroke (CS). However, the procedure
may be associated with cardiac complications. Transoesophageal
echocardiography (TOE), despite its limitations, is considered the ‘gold
standard’ for PFO diagnosis but an unequivocal diagnostic algorithm for
the detection of PFO and its treatment is still lacking. The Pascal
classification system recommends PFO closure plus antiplatelet therapy
in selected patients aged under 60 years (essentially those with a large
right-to-left shunt or an atrial septal aneurysm), without other
evident cause of stroke.
Summary: Exposure to long-wavelength red light
significantly reduced blood clot formation in both mice and human
studies. Red light was associated with lower inflammation, reduced
immune system activation, and fewer clot-promoting mechanisms, such as
neutrophil extracellular traps (NETs) and platelet activation.
Unlike
blue or white light, red light influenced clotting through optic
pathways, suggesting its effects are mediated by neural mechanisms
rather than direct blood exposure. These findings offer promising
implications for reducing risks of heart attacks, strokes, and other
clot-related conditions, particularly in high-risk groups like cancer
patients.
Researchers are developing red-light-based
interventions, such as goggles, to explore potential therapeutic
applications. If verified through clinical trials, this approach could
revolutionize clot prevention and save millions of lives.
Key Facts:
Clot Reduction: Mice exposed to red light had five times fewer blood clots than those exposed to blue or white light.
Mechanism: Red light reduced inflammation and platelet activation, key drivers of clot formation.
Human Connection: Cancer patients with blue light-filtering lenses also showed lower blood clot risks.
Source: University of Pittsburgh
Humans
and mice exposed to long-wavelength red light had lower rates of blood
clots that can cause heart attacks, lung damage and strokes, according
to research led by University of Pittsburgh School of
Medicine and UPMC surgeon-scientists and published today in the Journal of Thrombosis and Haemostasis.
The
findings, which need to be verified through clinical trials, have the
potential to reduce blood clots in veins and arteries, which are leading
causes of preventable death worldwide.
The
team observed that red light exposure is associated with less
inflammation and activation of the immune system. Credit: Neuroscience
News
“The light we’re exposed to can change our biological processes and
change our health,” said lead author Elizabeth Andraska, M.D., assistant
professor of surgery in Pitt’s Trauma and Transfusion Medicine Research
Center and vascular surgery resident at UPMC. “Our findings could lead
to a relatively inexpensive therapy that would benefit millions of
people.”
Scientists have long connected light exposure to health
outcomes. The rising and setting of the sun underlies metabolism,
hormone secretion, even the flow of blood, and heart attacks and
stroke are more likely to happen in the morning hours than at night.
Andraska and her colleagues wondered if light could have an impact on
the blood clots that lead to these conditions.
To test this idea,
the team exposed mice to 12 hours of either red, blue or white light,
followed by 12 hours of darkness, in a 72-hour cycle. They then looked
for differences in blood clots between the groups.
The mice
exposed to red light had nearly five times fewer clots than the mice
exposed to blue or white light. Activity, sleep, eating, weight and body
temperature remained the same between the groups.
The
team also analyzed existing data on more than 10,000 patients who had
cataract surgery and received either conventional lenses that transmit
the entire visible spectrum of light, or blue light-filtering lenses,
which transmit about 50% less blue light.
They discovered that cancer patients who received blue
light-filtering lenses had lower risk of blood clots compared to their
counterparts with conventional lenses. This is especially notable
because cancer patients have nine times the risk of blood clots of
non-cancer patients.
“These results are unraveling a fascinating
mystery about how the light to which we’re exposed on a daily basis
influences our body’s response to injury,” said senior author Matthew
Neal, M.D., professor of surgery, Watson Fund in Surgery Chair and
co-director of the Trauma and Transfusion Medicine Research Center at
Pitt, and trauma surgeon at UPMC.
“Our next steps are to figure
out why, biologically, this is happening, and to test if exposing people
at high risk for blood clots to more red light lowers that risk.
Getting to the bottom of our discovery has the potential to massively
reduce the number of deaths and disabilities caused by blood clots
worldwide.”
The recently published study indicates that the optic
pathway is key – light wavelength didn’t have any impact on blind mice,
and shining light directly on blood also didn’t cause a change in
clotting.
The team observed that
red light exposure is associated with less inflammation and activation
of the immune system. For example, red light-exposed mice had fewer
neutrophil extracellular traps – aptly abbreviated as “NETs” – which are
web-like structures made by immune cells to trap invading
microorganisms. They also trap platelets, which can lead to clots.
The mice exposed to red light also had increased fatty acid
production, which reduces platelet activation. Since platelets are
essential to forming clots, this naturally leads to less clot formation.
Understanding
how the red light is triggering changes that lower clotting risk could
also put scientists on the track of better medications or therapies that
could be more potent and convenient for patients than continuous red
light exposure.
In preparation for clinical trials, the team is
developing red light goggles to control the amount of light exposure
study participants receive and investigating who may most benefit from
red light
Additional authors on this research are Frederik
Denorme, Ph.D., Robert Campbell, Ph.D., and Matthew R. Rosengart, M.D.,
all of Washington University in St. Louis; Christof Kaltenmeier, M.D.,
Aishwarrya Arivudainabi, Emily P. Mihalko, Ph.D., Mitchell Dyer, M.D.,
Gowtham K. Annarapu, Ph.D., Mohammadreza Zarisfi, M.D., Patricia
Loughran, Ph.D., Mehves Ozel, M.D., Kelly Williamson, Ph.D., Roberto
Mota-Alvidrez, M.D., Sruti Shiva, Ph.D., Susan Shea, Ph.D., and Richard
A. Steinman, M.D., Ph.D., all of Pitt; and Kimberly Thomas, Ph.D.,
of Vitalant Research Institute.
Funding: This
research was supported by National Institutes of Health grants
R35GM119526, K01AG059892, R01HL163019, R01GM147121, R01GM145674,
T32HL98036 and S10OD028483, the University of Pittsburgh Center for
Research Computing, National Center for Research Resources Shared
Instrumentation grants 1S10OD016232-01, 1S10OD018210-01A1 and
1S10OD021505-01, American Heart Association 2021Post830138 award, and a
Physician-Scientist Institutional Award from the Burroughs Wellcome
Fund.
FYI. But they still asked for additional research. Since we have NO strategy to update and NO leadership to contact, NOTHING WILL BE DONE. That is how bad the failures are in the stroke medical world,
A
large proportion of ischemic stroke patients lack a definitive stroke
etiology despite extensive diagnostic testing. Varicella-Zoster Virus
(VZV) can directly invade blood vessels causing vasculitis and may be
associated with cryptogenic stroke (CS).
Methods:
We
conducted a retrospective cross-sectional study of CS patients tested
for VZV. The following were considered evidence of VZV reactivation
(VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG
CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+
proportion with 95% confidence intervals (CI) determined with the Wald
method, and compare patient groups using standard statistical tests.
Results:
A
total of 72 CS patients met full study inclusion criteria. Most of the
patients were <65 years old, had few traditional vascular risk
factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and
47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had
evidence of CNS VZV reactivation. There was no difference in evaluated
demographic or radiographic features between those with versus without
evidence of VZV reactivation. History of ischemic stroke in the past
year (11/14 vs 25/43, P<.05) and hypertension (13/14 vs 35/58 and P<.05) were associated with VZV+.
Conclusion:
We
found a high proportion of CNS VZV reactivation in a cross-sectional
cohort of CS patients selected for CSF testing. Testing for VZV might be
reasonable in CS patients who are young, have multifocal infarcts, or
had an ischemic stroke within the past year, but additional research is
needed.
Takao Hoshinohttps://orcid.org/0000-0002-2477-9755, Takafumi Mizuno, Ayako Nishimura, Kentaro Ishizuka, Sono Toi, Shuntaro Takahashi, Sho Wako, and Kazuo Kitagawahttps://orcid.org/0000-0002-7669-231X
Background:
Common vascular diseases underlying stroke, including atherosclerosis, small-vessel disease (SVD), and cardioembolic pathology, can be present in patients with embolic stroke of undetermined source (ESUS), although these are not direct causes of stroke. Aims:To describe the frequency and degree of the three major diseases using atherosclerosis, SVD, cardiac pathology, other causes, and dissection (ASCOD) phenotyping and to assess their prognostic implications in ESUS.
Methods:
In this prospective observational study, 221 patients with ESUS within 1 week of onset were consecutively enrolled and followed up for 1 year. Vascular diseases associated with stroke were assessed using the ASCOD classification. The primary outcome was a composite of nonfatal stroke, nonfatal acute coronary syndrome, and vascular death.
Results:
Among 221 patients (mean age, 69.6 years; male, 59.7%), 135 (61.1%), 102 (46.2%), and 107 (48.4%) had any grade of atherosclerosis (A2 or A3), SVD (S3), and cardiac pathology (C2 or C3), respectively. ESUS patients graded as A2 or A3 (i.e. ipsilateral atherosclerotic plaque, contralateral ⩾ 50% stenosis, or aortic arch plaque) were at a significantly higher risk of composite vascular events than those graded as A0 (i.e. no atherosclerotic disease) (adjusted hazard ratio (95% confidence interval), 2.40 (1.01–5.72). No differences were observed in the event risk between patients with S3 (i.e. magnetic resonance imaging evidence of SVD) and S0 (i.e. no SVD) and between those with C2 or C3 (i.e. presence of any cardiac pathology) and C0 (i.e. no cardiac abnormalities).
Conclusions:
Atherosclerotic diseases corresponding to ASCOD grade A2 or A3 were predictive of recurrent vascular events in ESUS patients. Reclassification of ESUS using ASCOD phenotyping provides important clues for risk prediction and may guide optimal management strategies. Keywords ASCOD, atherosclerosis, cardioembolism, embolic stroke of undetermined source, etiology, small vessel disease Department of Neurology, Tokyo Women’s Medical University Hospital, Tokyo, Japan Corresponding author(s): Takao Hoshino, Department of Neurology, Tokyo Women’s Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Email: hoshino.takao@twmu.ac.jp
Good luck understanding anything here. But the takeaway is to not have a cryptogenic stroke since your doctor has nothing to prevent the next one.
Nomogram: diagram representing the relations between three
or more variable quantities by means of a number of scales, so arranged
that the value of one variable can be found by a simple geometric
construction, for example, by drawing a straight line intersecting the
other scales at the appropriate values.
Zhuonan Wu1†, Chuanjing Zhang2†, Nan Liu3, Wenqing Xie3, Jinjin Yang4, Hangyuan Guo5 and Jufang Chi5*
1Shaoxing University School of Medicine, Shaoxing, China
2Ningbo University School of Medicine, Ningbo, China
3Zhejiang Chinese Medical University of Medicine, Hangzhou, China
4Zhejiang University School of Medicine, Hangzhou, China
5Department of Cardiology, The First Affiliated Hospital of Shaoxing University (Shaoxing People's Hospital), Shaoxing, China
Background: The high prevalence of
patent foramen ovale (PFO) in cryptogenic stroke suggested a
stroke-causing role for PFO. As risk factors for recurrence of such
stroke are not recognized, clinicians cannot sufficiently identify,
treat, and follow-up high-risk patients. Therefore, this study aimed to
establish a prediction model for PFO-related stroke recurrence.
Methods: This study included 392
patients with PFO-related stroke in a training set and 164 patients with
PFO-related stroke in an independent validation set. In the training
set, independent risk factors for recurrence identified using forward
stepwise Cox regression were included in nomogram 1, and those
identified using least absolute shrinkage and selection
operator(LASSO)regression were included in nomogram 2. Nomogram
performance and discrimination were assessed using the concordance index
(C-index), area under the curve (AUC), calibration curve, and decision
curve analyses (DCA). The results were also validated in the validation
set.
Results: Nomogram 1 was based on
homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP), and
albumin (ALB), and nomogram 2 was based on age, diabetes, hypertension,
right-to-left shunt, ALB, prealbumin, hsCRP, and Hcy. The C-index of
nomogram 1 was 0.861, which was not significantly different from that of
nomogram 2 (0.893). The 2- and 5-year AUCs of nomogram 1 were 0.863 and
0.777, respectively. In the validation set, nomogram 1 still had good
discrimination (C-index, 0.862; 2-year AUC, 0.839; 5-year AUC, 0.990).
The calibration curve showed good homogeneity between the prediction by
nomogram 1 and the actual observation. DCA demonstrated that nomogram 1
was clinically useful. Moreover, patients were successfully divided into
two distinct risk groups (low and high risk) for recurrence rate by
nomogram 1.
Conclusions: Nomogram 1, based on Hcy,
hsCRP, and ALB levels, provided a more clinically realistic prognostic
prediction for patients with PFO-related stroke. This model could help
patients with PFO-related stroke to facilitate personalized prognostic
evaluations.
Introduction
Approximately 30–40% of ischemic strokes are known as “cryptogenic strokes” because they have no identified cause (1).
In the last century, epidemiological surveys have found a significantly
higher prevalence of patent foramen ovale (PFO) in the cryptogenic
stroke population than in the normal population, suggesting a
stroke-causing role for PFO (2).
The main mechanism of PFO-related stroke is currently believed to be
paradoxical embolism, in which a thrombus from the vein (especially the
deep vein of the lower extremity) travels through the venous system to
the right atrium and through the PFO to the left atrium, which is known
as a right-to-left shunt (RLS), then the thrombus followed by blood flow
into cerebral arteries, leading to stroke. In 2017, the publication of
the results of the RESPECT long-term follow-up, the CLOSE trial, and the
Gore-REDUCE trial verified that PFO can cause stroke and strongly
demonstrated that PFO closure is superior to drug treatment alone in
reducing the recurrence of PFO-related stroke (3–5). Consequently, scholars formally proposed the concept of “PFO-related stroke” in 2020 (6).
Although PFO closure resulted in a relative (65%) reduction in the risk
of stroke recurrence compared with antiplatelet treatment alone (7),
the relatively low absolute recurrence rate of PFO-related stroke
itself and the lack of accurate assessment of patient prognosis allow
that a large number of patients remain on conservative drug therapy and
some even remain untreated. Despite the absence of data on the long-term
risk of stroke recurrence (>10 years) in patients with PFO-related
stroke receiving drug therapy, more than 50% of patients were followed
up for 5 years or longer. In these trials (3),
the Kaplan-Meier curves for drug treatment did not show a decrease in
the rate of stroke recurrence over time. In some studies, the annual
recurrence rate of PFO-related stroke remained as high as approximately
4.8%, and this figure even increased to 8.2% in some patients with
PFO-related stroke (8).
Therefore, it is essential to identify the population at a high risk of
PFO-related stroke recurrence, which is also a current clinical
limitation. There is no consensus regarding risk factors for PFO-related
stroke recurrence or clinically available biological markers. Although
some studies have identified larger PFO size, larger RLS, atrial septal
aneurysm (ASA), and high homocysteine (Hcy) levels as risk factors for
PFO-related stroke recurrence, there is still a lack of consistent
understanding and integration of risk scores for each independent risk
factor.
So you described something, WHAT THE FUCK DO SURVIVORS DO WITH IT TO PREVENT THE NEXT STROKE? Nothing? Then totally useless research. The mentors and senior researchers need re-education in the point of stroke research. 100% RECOVERY!
Takao Hoshinohttps://orcid.org/0000-0002-2477-9755, Takafumi Mizuno, Ayako Nishimura, Kentaro Ishizuka, Sono Toi, Shuntaro Takahashi, Sho Wako, and Kazuo Kitagawahttps://orcid.org/0000-0002-7669-231X Background:
Common vascular diseases underlying stroke, including atherosclerosis, small-vessel disease (SVD), and cardioembolic pathology, can be present in patients with embolic stroke of undetermined source (ESUS), although these are not direct causes of stroke.
Aims:
To describe the frequency and degree of the three major diseases using atherosclerosis, SVD, cardiac pathology, other causes, and dissection (ASCOD) phenotyping and to assess their prognostic implications in ESUS.
Methods:
In this prospective observational study, 221 patients with ESUS within 1 week of onset were consecutively enrolled and followed up for 1 year. Vascular diseases associated with stroke were assessed using the ASCOD classification. The primary outcome was a composite of nonfatal stroke, nonfatal acute coronary syndrome, and vascular death.
Results:
Among 221 patients (mean age, 69.6 years; male, 59.7%), 135 (61.1%), 102 (46.2%), and 107 (48.4%) had any grade of atherosclerosis (A2 or A3), SVD (S3), and cardiac pathology (C2 or C3), respectively. ESUS patients graded as A2 or A3 (i.e. ipsilateral atherosclerotic plaque, contralateral ⩾ 50% stenosis, or aortic arch plaque) were at a significantly higher risk of composite vascular events than those graded as A0 (i.e. no atherosclerotic disease) (adjusted hazard ratio (95% confidence interval), 2.40 (1.01–5.72). No differences were observed in the event risk between patients with S3 (i.e. magnetic resonance imaging evidence of SVD) and S0 (i.e. no SVD) and between those with C2 or C3 (i.e. presence of any cardiac pathology) and C0 (i.e. no cardiac abnormalities).
Conclusions:
Atherosclerotic diseases corresponding to ASCOD grade A2 or A3 were predictive of recurrent vascular events in ESUS patients. Reclassification of ESUS using ASCOD phenotyping provides important clues for risk prediction and may guide optimal management strategies.
Vascular
diseases underlying stroke, including atherosclerosis, small-vessel
disease (SVD), and cardioembolic pathology, can be present in patients
with embolic stroke of undetermined source (ESUS), although these are
not direct causes of stroke.
Aims:
To describe the
frequency and degree of the 3 major diseases using ASCOD phenotyping and
to assess their prognostic implications in ESUS.
Methods:
In
this prospective observational study, 221 patients with ESUS within 1
week of onset were consecutively enrolled and followed up for 1 year.
Vascular diseases associated with stroke were assessed using the ASCOD
classification. The primary outcome was a composite of major adverse
cardiovascular events (MACEs).
Results:
Among 221
patients, 135 (61.1%), 102 (46.2%), and 107 (48.4%) had any grade of
atherosclerosis (A2 or A3), SVD (S3), and cardiac pathology (C2 or C3),
respectively. ESUS patients graded as A2 or A3 (i.e., ipsilateral
atherosclerotic plaque, contralateral ≥50% stenosis, or aortic arch
plaque) were at a significantly higher risk of MACE than those graded as
A0 (i.e., no atherosclerotic disease) (adjusted hazard ratio [95%
confidence interval], 2.40 [1.01–5.72]). No differences were observed in
the event risk between patients with S3 (i.e., magnetic resonance
imaging evidence of SVD) and S0 (i.e., no SVD) and between those with C2
or C3 (i.e., presence of any cardiac pathology) and C0 (i.e., no
cardiac abnormalities).
Conclusions:
ASCOD grade A2
or A3 was predictive of MACE in ESUS patients. Reclassification of ESUS
using ASCOD phenotyping provides important clues for risk prediction and
may guide optimal management strategies.
The
effect of interventions on functional impairment is an important
outcome in stroke prevention trials and should be considered as an
adjunct to counting discrete events. In the NAVIGATE-ESUS trial, 7213
patients with recent embolic strokes of undetermined source were
randomized to rivaroxaban (15 mg once daily) or aspirin (100 mg daily).
After 11 months there was no effect on the prevention of recurrent
stroke.
Aims
To determine the effect of rivaroxaban compared to aspirin on functional and cognitive outcomes.
Methods
Function
and cognition were measured at baseline, 1 year, and study end using
the Standard Assessment of Global Everyday Activities (SAGEA), a 15-item
scale assessing cognitive, instrumental, and basic activities of daily
living as well as mobility, and the Montreal Cognitive Assessment
(MoCA). Changes in scores were calculated by subtracting either study
end or 1-year scores from baseline, and differences in distributions
were compared using the Mann-Whitney U test. SAGEA and MoCA scores were
also correlated with recurrent stroke.
Results
Follow-up
SAGEA scores were available in 6378 (88%) participants. There was no
difference in change in function for those allocated to rivaroxaban
compared to aspirin (Mann-Whitney U test, p = 0.8), with both
distributions having a median (25p,75p) change of 0 (-2,1). Overall,
more of those who experienced a recurrent stroke (n=247; mostly minor
ischemic), reported functional difficulty at study end versus entry,
compared with those who did not (51% versus 30%, chi-square test, p<
0.001), and this was consistent across global regions. There was no
difference in the change in cognition by treatment group, nor were
recurrent strokes associated with a change in cognition.
Conclusions
Rivaroxaban,
compared to aspirin, was not associated with changes in functional or
cognitive status in patients with recent ESUS. The SAGEA scale detected
changes in functional status associated with recurrent strokes in an
international stroke population.
You can't let your doctor get by with not figuring out THE EXACT REASON FOR YOUR STROKE. Damned difficult to prevent the next one if your doctor fails at finding the reason.
Cryptogenic
stroke represents a heterogenous but clinically important collection of
stroke etiologies for which our understanding continues to grow. Here,
we review our current knowledge and most recent recommendations on
secondary prevention for common causes of cryptogenic stroke including
paroxysmal atrial fibrillation, atrial cardiopathy, patent foramen
ovale, and substenotic atherosclerotic disease as well as the
under-recognized mechanisms of occult malignancy, heart failure, and,
most recently, infection with severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2).
Recent Findings
The
results from recent observational studies and randomized clinical
trials have provided greater insight into the causal relationship and
attributable risk of these suspected etiologies and have identified
potential strategies to reduce the rates of recurrence. However, further
clinical trials are needed to confirm the benefits of specific stroke
prevention strategies, including the patient populations most likely to
benefit from anticoagulation.
Summary
There
is ongoing research aimed at both reducing the proportion of ischemic
strokes classified as cryptogenic and resolving much of the clinical
equipoise that still exists. The results of these studies have the
potential to provide us with a better understanding of these occult
mechanisms and allow for more targeted interventions.
Introduction
Ischemic
strokes can result from several different mechanisms, the majority of
which can be readily identified following a standard diagnostic
evaluation. However, in about 25% of cases stroke etiology remains
unknown—a clinically important point as the effectiveness of secondary
prevention strategies often hinges on accurate and timely identification
of the underlying cause [1].
Our understanding of cryptogenic stroke has evolved through the years
and depends on the classification system used. An early and commonly
used system arose from the TOAST (Trial of Org 10,172 in Acute Stroke
Treatment) study which classified ischemic strokes based on five
potential etiologies: [1] large artery atherosclerosis, [2] cardioembolism, [3] small vessel occlusion, [4] other determined etiology (e.g., dissection), or [5] of undetermined source (i.e., cryptogenic) [2]. According to the TOAST system, strokes could be classified as cryptogenic [1] after an extensive evaluation, [2] after an incomplete evaluation, or [3]
due to the presence of multiple competing etiologies. The simplicity of
the system has made it widely popular for use in both clinical practice
and scientific research. However, through the years, as stroke research
has evolved (along with our standards for optimal care), TOAST’s broad
inclusion criteria for cryptogenic stroke has complicated efforts
towards targeted medical management. Since then additional
classification systems have been developed, emphasizing underlying
mechanisms (causative) and/or disease manifestations (phenotypic) (Table
1) [2,3,4].
In an attempt to identify a single and therapeutically distinct subset
of patients with cryptogenic stroke, Hart and colleagues proposed the
concept of ESUS, or embolic stroke of undetermined source, broadly
defined as nonlacunar brain infarcts occurring in the absence of [1] ≥ 50% luminal atherosclerotic stenosis of the supplying extracranial or intracranial arteries, [2] any major-risk cardioembolic source, and [3] any other specific cause of stroke (e.g., dissection, vasospasm, drug abuse) [5].
With this distinction, the authors proposed there was likely a subset
of cryptogenic strokes that were more likely embolic in origin and
perhaps more likely to respond to anticoagulant therapy. However, even
with these new constructs, cryptogenic stroke remains a diagnostic
challenge. As the 10-year risk of recurrence is estimated to be as high
as 30%, investigations into potential sources of cryptogenic stroke
should be focused and deliberate—guided by patient factors and clinical
features aimed at increasing the yield of diagnostic studies and
identifying patients who would likely benefit from targeted therapies [6].
Table 1 Summary of ischemic stroke classification systems
In
the last 5 years, several clinical trials have investigated the
efficacy of newer therapies for specific conditions often implicated in
cryptogenic stroke. Non-vitamin K oral antagonists (NOACs), such as
dabigatran, rivaroxaban, and apixaban have been explored in patients
with ESUS, heart failure, and malignancy with varying degrees of success
[7, 8••, 9•].
The results of these studies have inspired additional trials using
these new agents in more select sub-populations. In addition, the recent
CLOSE, REDUCE, and DEFENSE-PFO studies identified patients with
cryptogenic stroke and PFO who may benefit most from PFO closure,
prompting a recent update in the recommendations from the American
Academy of Neurology [10,11,12].
Although these discoveries highlight recent progress in the area of
cryptogenic stroke, their gaps and limitations emphasize the need for
continued work into interventions that may further reduce the risk of
recurrence in these special populations.
This obviously means your doctors and stroke hospitals are not providing any information to a central database of stroke outcomes. The failure on that is directly tied to our fucking failures of stroke associations doing nothing useful.
There
are scarce data regarding the prevalence, characteristics and outcomes
of intracerebral hemorrhage (ICH) of undetermined (unknown or
cryptogenic) etiology. We sought to determine the prevalence,
radiological characteristics, and clinical outcomes of undetermined ICH.
Methods:
Systematic
review and meta-analysis of studies involving patients with spontaneous
ICH was conducted to primarily assess the prevalence and
clinical-radiological characteristics of undetermined ICH. Additionally,
we assessed the rates for ICH secondary to hypertensive arteriopathy
and cerebral amyloid angiopathy. Subgroup analyses were performed based
on the use of (1) etiology-oriented ICH classification, (2) detailed
neuroimaging, and (3) Boston criteria among patients with cerebral
amyloid angiopathy related ICH. We pooled the prevalence rates using
random-effects models, and assessed the heterogeneity using Cochran Q and I2 statistics.
Results:
We
identified 24 studies comprising 15 828 spontaneous ICH patients (mean
age, 64.8 years; men, 60.8%). The pooled prevalences of hypertensive
arteriopathy ICH, undetermined ICH, and cerebral amyloid angiopathy ICH
were 50% (95% CI, 43%–58%), 18% (95% CI, 13%–23%), and 12% (95% CI,
7%–17% [P<0.001 between subgroups]). The volume of ICH was the
largest in cerebral amyloid angiopathy ICH (24.7 [95% CI, 19.7–29.8]
mL), followed by hypertensive arteriopathy ICH (16.2 [95% CI, 10.9–21.5]
mL) and undetermined ICH (15.4 [95% CI, 6.2–24.5] mL). Among patients
with undetermined ICH, the rates of short-term mortality (within 3
months) and concomitant intraventricular hemorrhage were 33% (95% CI,
25%–42%) and 38% (95% CI, 28%–48%), respectively. Subgroup analysis
demonstrated a higher rate of undetermined ICH among studies that did
not use an etiology-oriented classification (22% [95% CI, 15%–29%]). No
difference was observed between studies based on the completion of
detailed neuroimaging to assess the rates of undetermined ICH (P=0.62).
Conclusions:
The
etiology of spontaneous ICH remains unknown or cryptogenic among 1 in 7
patients in studies using etiology-oriented classification and among 1
in 4 patients in studies that avoid using etiology-oriented
classification. The short-term mortality in undetermined ICH is high
despite the relatively small ICH volume.
Ischemic stroke has been reported in various conditions associated with eosinophilia. FIP1L1-PDGFRA fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; F/P)
leads to the proliferation of the eosinophilic lineage and thus to a
clonal hypereosinophilic syndrome that is highly responsive to imatinib.
Methods:
We previously reported on a nationwide retrospective study of 151 patients with F/P-associated
clonal hypereosinophilic syndrome. Patients from this cohort with a
clinical history of ischemic stroke (as well as 2 additional cases) were
further analyzed to better define their clinical picture and outcomes.
Results:
Sixteen
male patients (median age, 51 [43–59] years) with low-to-intermediate
cardiovascular risk were included. Median National Institutes of Health
Stroke Scale was 4 (range, 1–6). Most cerebral imaging disclosed
multiple bilateral infarctions of watershed distribution (69%). Despite
frequent cardiac involvement (50%), cardiac thrombus was evidenced in a
single patient and, according to the TOAST classification (Trial of ORG
10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of
undetermined etiology. Among the 15 patients treated with imatinib, and
after a median follow-up of 4.5 years, stroke recurred in only 3
patients (consisting of either cardio embolic or hemorrhagic events,
unrelated to the first episode).
Conclusions:
F/P+
clonal hypereosinophilic syndrome is a diagnosis to consider in
patients with unexplained ischemic stroke and hypereosinophilia
(especially in the setting of multiple cortical borderzone distribution)
and warrants prompt initiation of imatinib.
Just because you can't explain the cause of the stroke doesn't absolve you of the responsibility to get your survivors 100% recovered. YOUR DOCTOR'S RESPONSIBILITY! Don't let them weasel out of getting you 100% recovered. There are NO EXCUSES ALLOWED!
Embolic
stroke of undetermined source (ESUS) accounts for up to 25% of strokes.
Understanding risk factors associated with ESUS is important in
reducing stroke burden worldwide. However, ESUS patients are younger and
present with fewer traditional risk factors. Significant global
variation in ESUS populations also exists making the clinical picture of
this type of stroke unclear.
Methods and results
ESUS patients were pair matched for age, sex, and ethnicity with a group of all other strokes (both n = 331).
Exploratory factor analysis was applied in both groups to 14 risk and
clinical factors to identify latent factors. In ESUS patients, two
latent factors emerged consisting primarily of heart-related variables
such as left ventricular wall motion abnormalities, reduced ejection
fraction, and increased left atrial volume index, as well as aortic arch
atherosclerosis. This is in comparison to the all other strokes group,
which was dominated by traditional stroke risk factors.
Conclusions
Our
findings support the existence of a unique pattern of risk factors
specific to ESUS. We show that LVWMA and corresponding changes in left
heart function are a potential source of emboli in these patients. In
addition, the clustering of aortic arch atherosclerosis with left heart
factors suggests a causal link. Through the application of exploratory
factor analysis, this work contributes to a further understanding of
stroke mechanisms in ESUS.
Since its formal characterization,1
embolic stroke of undetermined source (ESUS) has generated much
interest. Several risk factors have been associated with an ESUS
diagnosis, such as aortic arch atherosclerosis,2 hypertension,3 and left ventricular wall motion abnormalities (LVWMA).4 However, the clinical picture of ESUS remains unclear with covert atrial fibrillation the most widely speculated upon cause.5,6
One
of the difficulties in identifying risk profiles for ESUS patients is
the consistent finding that they are younger and carry fewer traditional
risk factors than other forms of stroke diagnosis.7 Another difficulty is the global variation in ESUS populations, likely stemming from genetic and culturally determined factors.8,9
In addition, the majority of work on this topic uses multivariate
statistics to show how risk factors differ from other forms of stroke
diagnoses (or normal populations) but not how they manifest in ESUS only
populations.
To address these issues, this study applies
exploratory factor analysis to investigate the interactions between risk
factors for ESUS while controlling for age, sex, and ethnicity.
Exploratory factor analysis assesses underlying interactions between variables and specifies latent factors.10
Latent (meaning “hidden”) variables are unobserved but identified
through shared features of observed variables. The usefulness of
understanding risk factor interactions in this way is highlighted by
metabolic syndrome, whereby vascular risk and metabolic
abnormalities combine to confer increased cerebro- and cardiovascular
hazard.11
To our knowledge, no studies have explored similar clustering of risk
factors in ESUS patients and this work is the first to do so.
Zhuonan Wu1†, 
Hangyuan Guo
Jufang Chi
