Arterial widening emerges as key driver of small vessel stroke

 How will this change your competent? doctors' protocols on treating stroke? Oh, nothing will happen because there are NO protocols, since your doctor is guessing every step of the way, Hope the guesses are correct because your doctor gets paid regardless!

Arterial widening emerges as key driver of small vessel stroke

A prospective study of 229 patients with lacunar or mild non-lacunar stroke found that large-artery stenosis was not associated with cerebral small-vessel disease (cSVD) or incident infarcts, whereas arterial widening and basilar artery dolichoectasia were strongly linked to lacunar stroke, higher cSVD burden, and progression of brain lesions over 1 year.

The findings, published in Circulation, challenge traditional atherosclerotic paradigms and suggest that intrinsic microvascular pathology plays a central role in cSVD, underscoring the need for mechanism-specific diagnostic and therapeutic strategies in stroke care.

“This study provides strong evidence that lacunar stroke is not caused by fatty blockage of larger arteries, but by disease of the small vessels within the brain itself,” said Joanna Wardlaw, University of Edinburgh’s Institute for Neuroscience and Cardiovascular Disease, Edinburgh, United Kingdom. “Recognising this distinction is crucial, because it explains why conventional treatments like antiplatelet drugs are not as effective for this type of stroke and highlights the urgent need to develop new therapies that target the underlying microvascular damage.”

For the study, the researchers followed 229 patients (mean age, 65.9 years; 57% with lacunar stroke) with serial clinical and MRI assessments over 1 year to evaluate the impact of large-artery stenosis and arterial widening on stroke subtype and cSVD. Large-artery stenosis (≥50%) was present in 20.5% of patients and basilar artery dolichoectasia in 15.7%, with multivariable analyses adjusting for demographic and vascular risk factors.

Results showed that large-artery stenosis was not associated with cSVD markers or incident infarcts and was instead linked to lower odds of lacunar versus non-lacunar stroke (odds ratio [OR] = 0.49), whereas basilar artery dolichoectasia was strongly associated with lacunar stroke (OR = 4.67), higher small-vessel disease burden (OR = 2.57), increased risk of incident infarcts (OR = 2.29; 75% subcortical), and greater progression of white matter hyperintensities over 1 year (β 0.15 per log10 volume increase).

The researchers said that future treatments should target the underlying small vessel damage. Trials such as LACI-3 are now testing whether existing drugs, including cilostazol and isosorbide mononitrate, can protect the brain, reduce further strokes, and help prevent problems with memory, mobility, and dementia after lacunar stroke.

Reference: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079493

SOURCE: University of Edinburgh

Combination of Two Common Cariovascular Drugs Could Improve Outcomes in Lacunar Stroke

Well then write up a proposed protocol on this and get it distributed to all stroke hospitals in the world AND ENSURE staff doctors get trained in its' use. 

Combination of Two Common Cariovascular Drugs Could Improve Outcomes in Lacunar Stroke

Two commonly used cardiovascular medications were safe and well tolerated by patients who had experienced a small vessel stroke, according to results from the open-label, phase 2, randomized Lacunar Intervention Trial-2 (LACI-2) published May 24 in JAMA Neurology.

The trial also showed signs that the drug combination could potentially improve cognitive outcomes in lacunar stroke, although larger trials will be needed to confirm these findings.

LACI-2, the second largest trial ever in lacunar stroke, was designed to assess the feasibility, drug tolerability, safety, and effects of one year of treatment with isosorbide mononitrate (ISMN) and cilostazol on vascular, functional, and cognitive outcomes in patients with this type of stroke.

Lacunar stroke, which occurs in the small penetrating arteries deep within the brain, causes approximately 25 percent of ischemic strokes and is associated with significant morbidity and mortality, including major physical and cognitive disabilities. There is no proven treatment to improve outcomes after a lacunar stroke.

“There appeared to be some potential benefits that will need to be confirmed in a larger phase 3 trial," lead author Joanna M. Wardlaw, MD, FAHA, said at a presentation of the LACI-2 preliminary results during the American Stroke Association's International Conference in February 2023.

“We saw good hints of efficacy, particularly for isosorbide mononitrate on reducing recurrent stroke and cognitive impairment, and we also found that both medications together seemed to work synergistically, rather than counteracting any benefit," said Dr. Wardlaw, professor of applied neuroimaging, honorary consultant neuroradiologist, head of neuroimaging sciences, and director of Edinburgh Imaging at Edinburgh University in Scotland. “This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small vessel disease strokes. So, we cautiously hope that these medications may have wider implications for other types of small vessel disease."

Study Details

Between February 2018 and May 2022, the LACI-2 investigators enrolled 363 adults who had experienced lacunar stroke from 26 stroke centers across the United Kingdom. In addition to their standard prescribed stroke medications, study participants were randomized to a year in one of four treatment groups: 40 to 60 mg/day of oral ISMN alone, 200 mg/day of oral cilostazol alone, both medications, or neither medication. 

Participants in the LACI-2 trial had characteristics typical of lacunar ischemic stroke, including being younger compared with all patients with stroke; additionally, “more were men, few strokes had embolic sources, and patients had low rates of dependence and death (1.3 percent) but high rates of cognitive impairment (58.9 percent)."

Participants with indications for, or contraindications to, one study drug could be randomized to the other drug.

At one year, 358 of those initially enrolled were still participating in the study, with 95 percent of participants taking at least half of medication doses, meeting the study's feasibility outcome. The trial also met safety criteria, with relatively few adverse events.

Although the trial was not powered to evaluate efficacy, the composite efficacy outcome—which included vascular events, dependence, cognition, and death—showed signs of benefit with either of the drugs alone and a significantly lower rate with the combination compared with neither drug (48.6 percent vs. 69.6 percent). Overall, the absolute reduction in participants with any cognitive impairment was 18.7 percent (46.7 percent with ISMN-cilostazol and 65.4 percent with neither drug).

Individually, although it did not reduce the composite outcome, ISMN reduced recurrent stroke or transient ischemic attack (TIA)—2.2 percent with ISMN vs. 8.3 percent without; p=0.01)—and improved quality of life (p=0.03), reduced global Stroke Impact Scale (p=0.005), reduced global clinical outcomes (p=0.004), reduced cognitive impairment (p=0.008), and tended to reduce dependence. The absolute reduction in participants with any cognitive impairment was 10.4 percent (54.4 percent with ISMN and 64.8 percent without ISMN).

Cilostazol alone did not reduce the composite outcome, recurrent stroke, or TIA, nor did it improve quality of life or global clinical outcome. It did reduce dependence (with a modified Rankin Scale score of 3 to 6: 8.8 percent with cilostazol vs. 17.3 percent without; p=0.006). Cilostazol did not reduce cognitive impairment but tended to improve mood, as measured by the Zung depression scale (p=0.06).

“This is a great study and great news for the field of small vessel disease," said Jose Rafael Romero, MD, associate professor of neurology and a member of the Stroke Unit at Boston University Chobanian & Avedisian School of Medicine, which has  several ongoing clinical trials for acute stroke treatment and secondary prevention.

“There is a strong signal that there could be more targeted treatment for these patients, not only in stroke risk reduction but [also] with an apparent effect on cognitive outcomes. Small vessel disease is a major underlying cause of dementia, and I would argue that every type of dementia has some component of small vessel disease, so the public health impact of interventions like these can be enormous."

The successful achievement of the study's safety endpoint is strengthened by the fact that the two drugs were administered in addition to standard of care, including single or dual antiplatelet therapy. “In combination with those drugs, cilostazol and ISMN did not increase the risk of major bleeding and showed a safe profile, which makes these findings even stronger," Dr. Romero said.

The LACI-3 trial is now preparing to address many of these questions, and other trials are also being proposed to funders around the world.

“I'm very optimistic about these findings," Dr. Romero said. “I think they are likely to lead us toward a big change for the treatment of small vessel disease in a very positive way."

Look for more in-depth discussion in an upcoming issue of Neurology Today.

Disclosures

Dr. Romero had no disclosures.

Examining first treatment for strokes linked to dementia

Since you already have dementia when you get this stroke you'll have to hope like hell that your doctors are up-to-date on this treatment because you won't be able to inform them of this. Or better yet ask your doctor now to follow this since results are not expected for 5 years.

Examining first treatment for strokes linked to dementia

People who experience a type of stroke linked with nearly half of all dementias could be treated for the first time by repurposing two cheap and common drugs, a trial shows.

Researchers found that isosorbide mononitrate and cilostazol, which are already used to treat other heart and circulatory diseases, can safely improve the debilitating outcomes people experience after lacunar stroke.

The two drugs, which were found to be even more effective when used in combination, could be available as a treatment for lacunar strokes within five years, if the results are confirmed in further trials, experts say.

Lacunar strokes affect at least 35,000 people in the UK each year. They are caused by cerebral small vessel disease, where small blood vessels deep within the brain become damaged and stop working properly. Small vessel disease is also a common cause of cognitive impairment and dementia.

The strokes can be distressing as people may develop problems with their thinking and memory, movement, and even dementia. There are currently no specific effective treatments.

The trial, led by the Universities of Edinburgh and Nottingham and the UK Dementia Research Institute, involved 363 people who had experienced a lacunar stroke.

As well as their standard stroke prevention treatment, for one year participants took either isosorbide mononitrate or cilostazol individually, both drugs together, or neither.

The trial, funded by the British Heart Foundation, investigated cilostazol and isosorbide mononitrate as they possibly improve the function of the inner lining of blood vessels, which researchers believe play a role in small vessel disease.

Participants that took both drugs were nearly 20 per cent less likely to have problems with their thinking and memory compared to the group that did not take either drug. They were also more independent and reported a better quality of life.

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In addition, those who took isosorbide mononitrate were less likely to have had further strokes at one year than those who did not take the drug.

Taken on their own, isosorbide mononitrate also improved thinking and memory skills, and quality of life, while cilostazol improved independence and mood. These effects were strengthened when the two drugs were taken together, researchers say.

The team is now planning to test these drugs in a larger four-year clinical trial, which they hope to start by the end of 2023. They are also looking to test whether the drugs are effective in different conditions linked to small vessel disease, such as vascular cognitive impairment and dementia.

Now we understand more about what is triggering these small vessel strokes to attack the brain, we've been able to focus our efforts on treatments that can put a halt to this damage. We need to confirm these results in larger trials before either drug can be recommended as a treatment. However, as these drugs are already widely available for other circulatory disorders, and inexpensive, it shouldn't take too long to move our findings from research into everyday clinical practice."

Joanna Wardlaw, Professor and Chair, Applied Neuroimaging, University of Edinburgh

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said: "These promising findings provide a long-awaited positive step towards the first treatments becoming available for lacunar strokes, offering much needed hope for thousands of people. Lacunar strokes are not the only way that cerebral small vessel disease can affect someone. These findings also open new avenues of research into other conditions related to small vessel disease, such as vascular dementia."

Source:

University of Edinburgh

Journal reference:

Wardlaw, J. M., et al. (2023) The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial. JAMA. doi.org/10.1001/jamaneurol.2023.1526.

Familiar Drugs Get a Foot in the Door for Small Vessel Stroke Treatment

 So where is the protocol located so stroke patients can tell their stroke hospitals about it? I don't trust stroke hospitals to follow and implement research.

But this came out in May 2019 already! Did your incompetent hospital DO NOTHING WITH IT?

Cilostazol, Isosorbide Mononitrate Show Promise for Lacunar Stroke May 2019

 

Familiar Drugs Get a Foot in the Door for Small Vessel Stroke Treatment

Combined isosorbide mononitrate and cilostazol feasible, well tolerated in these patients

by Nicole Lou, Senior Staff Writer, MedPage Today February 9, 2023

DALLAS -- Drugs that improve endothelial function appeared promising for people with lacunar strokes resulting from small vessel disease (SVD), according to LACI-2 study findings that pave the way for a larger phase III trial.

Individuals taking isosorbide mononitrate and cilostazol together for a year following lacunar ischemic stroke had a significant reduction in the combined outcome of recurrent stroke, myocardial infarction, functional dependency, death, and cognitive impairment (48.6% vs 69.6% for controls not on either drug, adjusted HR 0.58, 95% CI 0.37-0.92).

While isosorbide mononitrate and cilostazol individually had no effect on the combined endpoint, isosorbide mononitrate in particular had a significant association with reduced recurrent strokes at 12 months (2.2% vs 8.3%, P=0.014), reported Joanna Wardlaw, MD, a neuroimaging specialist at the University of Edinburgh in Scotland, during the American Stroke Association's International Stroke Conferenceopens in a new tab or window (ISC).

What's more, safety events were rare in LACI-2. Extracranial hemorrhages were recorded in 1.1% of the cohort, intracranial hemorrhages in 0, and deaths in 1.1%. Moreover, there was no evidence of drug-drug interaction between isosorbide mononitrate and cilostazol.

Study findings suggest potential for a specific treatment for lacunar strokes, which account for up to a quarter of all ischemic stokes and are related to SVD of the brain. Affected patients are often left with cognitive impairment despite low dependency and stroke recurrence, according to Wardlaw.

Indeed, cognitive impairment was the major contributor to outcomes in the trial. As was the case with LACI-2's composite clinical result, only combination isosorbide mononitrate and cilostazol -- not either drug alone -- managed to reduce the risk of cognitive impairment, according to fellow LACI-2 investigator Philip Bath, DSc, a stroke specialist at the University of Nottingham in England.

"It is great to see that the combination treatment is safe and potentially effective ... It is exciting to see stroke prevention in small vessel disease moving forward," commented Shadi Yaghi, MD, a vascular neurologist at Brown University and Rhode Island Hospital in Providence, who was not involved with the study.

"It is difficult to draw conclusions, however, about the underlying pathophysiology of lacunar stroke based on the study, as cilostazol has also been suggested to be effective in patients with intracranial atherosclerosis as well," Yaghi cautioned in an email to MedPage Today.

It is believed that the intrinsic problem of lacunar strokes is tissue damage and impaired vasodilation in the small vessel endothelium. This is the rationale behind the hypothesis that endothelium-stabilizing drugs like isosorbide mononitrate and cilostazol might improve function and reduce damage.

Both drugs are widely available and inexpensive. Isosorbide mononitrate is a nitrate used to treat and prevent ischemic heart disease with no long-term data in stroke or cognition. Cilostazol is an antiplatelet and vasodilator preferred in Asia to prevent stroke.

Proving the benefit of the two agents will require a larger phase III trial. This LACI-3 trial is in preparation, Wardlaw told the ISC audience.

LACI-2 was conducted as a 2×2 factorial trial that had 363 adults randomized to one of four treatments for 1 year: 25-mg oral isosorbide mononitrate twice a day, 100-mg oral cilostazol twice a day, both medications, or neither medication. Doses were increased over 4 weeks to test tolerability.

Recruitment occurred at 26 stroke centers throughout the U.K. Eligible participants had a lacunar stroke and showed independent function. The cohort had a median age of 64 years, and approximately 31% were women. Groups were well balanced after randomization.

Nearly 90% of participants had a visible index infarct on imaging, the vast majority lacunar, with only 3% involving the middle cerebral artery or posterior cerebral artery.

Most patients were on antiplatelets (97%) and antihypertensives (76%) at baseline. Contraindications to either trial drug were noted in 12%.

LACI-2's overall results and cognition findings were consistent across prespecified subgroups.

The trial was nevertheless not powered for efficacy and subgroup analysis, and its data may be considered hypothesis-generating due to lack of adjustment for multiplicity. Other limitations included the open-label nature of the study and the issue of missing cognition data.

"We saw good hints of efficacy, particularly for isosorbide mononitrate on reducing recurrent stroke and cognitive impairment, and we also found that both medications together seemed to work synergistically, rather than counteracting any benefit," Wardlaw said.

"This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small vessel disease strokes. So, we cautiously hope that these medications may have wider implications for other types of small vessel disease," she added.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded primarily by the British Heart Foundation, with support from the U.K. Alzheimer's Society, the U.K. Dementia Research Institute, the Stroke Association, the Leducq Foundation, NHS Research Scotland, and the U.K. National Institutes of Health Research Clinical Research Networks.

Wardlaw and Yaghi had no disclosures.

Bath reported ties to CoMind, DiaMedica, Phagenesis, and Roche.

Primary Source

International Stroke Conference

Source Reference: opens in a new tab or windowWardlaw JM, et al "Cilostazol, isosorbide mononitrate and their combination to prevent recurrence and dependency in patients with small vessel stroke: the Lacunar Intervention Trial-2 (LACI-2)" ISC 2023.

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Two cardiovascular medicines were well-tolerated for small vessel stroke

Is your doctor and stroke hospital going to ensure this gets further human testing? NO? Then you don't have a functioning stroke doctor or hospital. I'd suggest firing the whole lot, starting with the board of directors, the rot starts at the top. 

Two cardiovascular medicines were well-tolerated for small vessel stroke

American Stroke Association International Stroke Conference – Late-Breaking Science Presentations LB4 and LB12

Research Highlights:

• No standard medical therapy exists for a stroke occurring in a small vessel in the deep areas of the brain — called a lacunar stroke.
• A preliminary study of two common cardiovascular medications, cilostazol and isosorbide mononitrate, suggests these two medications were safe and well-tolerated by adults who have experienced small vessel stroke, when taken alone or together.
• A larger, more extensive study is planned to examine the effectiveness of the medications in treating the complications of small vessel stroke.

Embargoed until 11:40 a.m. CT/12:40 p.m. ET Thursday, Feb. 9, 2023

DALLAS, Feb. 9, 2023 — A study of two widely used cardiovascular medications — cilostazol and isosorbide mononitrate — in more than 350 patients confirmed the two medications were well-tolerated and safe for people who have experienced a stroke in a small blood vessel deep in the brain. The results suggest the medications may help improve patient outcomes, according to preliminary late-breaking science presented today at the American Stroke Association’s International Stroke Conference 2023. The meeting, held in person in Dallas and virtually Feb. 8-10, 2023, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

Small vessel disease of the brain accounts for about 20% -25% of all ischemic strokes, according to previous research. A lacunar stroke, or small vessel stroke, occurs when the inner lining of the tiny blood vessels inside the brain are damaged, leading to a stroke or dementia.

“Currently, there is no proven treatment to prevent poor outcomes after lacunar stroke, so the ultimate goal with this research is to evaluate if medications with potential modes of action on the inner lining of blood vessels might help improve small vessel function and prevent or slow long-term brain damage after lacunar stroke,” said lead study investigator Joanna M. Wardlaw, M.D., FAHA, professor of applied neuroimaging, honorary consultant neuroradiologist, head of neuroimaging sciences and the director of Edinburgh Imaging at Edinburgh University in Edinburgh, Scotland. She is also the foundation chair of the U.K. Dementia Research Institute.

The medications in the study are commonly prescribed for other cardiac conditions. Isosorbide mononitrate is used to treat chest pain by relaxing blood vessels and decreasing blood pressure. Cilostazol improves the flow of blood by relaxing the blood vessels and reducing blood clotting. It is often prescribed for people with peripheral artery disease — a narrowing of the peripheral arteries that carry blood away from the heart to other parts of the body.

This study, called LACunar Intervention Trial 2 (LACI-2), is the second largest ever trial in lacunar stroke. It examined whether such a trial was feasible among people with lacunar strokes and if the medications would be well-tolerated for one year after lacunar stroke. Researchers also analyzed safety and other outcomes, including recurrent stroke, cognitive impairment, dependency, mood and quality of life. This detailed information is needed for the next stage of research – a phase 3 trial, which would include more study participants. Results of the analysis on cognitive status at one year will be presented separately in the same Main Event session on Feb. 9.

From Feb. 2018 to May 2022, researchers enrolled 363 adults who had experienced lacunar stroke from 26 stroke centers throughout the United Kingdom. The participants were average age 64 years, and 31% were women. All study participants continued to take their usual prescribed medications as per stroke guidelines, including those that reduce blood clotting, lower blood pressure and/or lower cholesterol — all of which may lower the risk of a second or recurrent stroke.

Participants were randomly assigned to one of four treatment groups: 40-60 mg/day of oral isosorbide mononitrate alone; 200 mg/day of oral cilostazol alone; both medications; or neither medication for one year. The participants completed phone surveys at 6 and 12 months to assess health status, including recurrent stroke and heart problems, cognitive tests, symptoms, quality-of-life surveys, and had brain imaging at 12 months.

The study met its initial goals to determine if a larger trial was feasible and if the medications were safe and tolerable. After one year, 358 of the adults were still participating in the study, with 95% of participants taking at least half of medication doses prescribed for the trial. Safety criteria were also met: four participants died; there were four episodes of bleeding outside of the brain; no excessive falls or dizziness. Some participants experienced mild symptoms (such as headaches), which were expected.

Researchers also saw some potential benefits from the medication groups, including data that indicated the group who took the combined isosorbide mononitrate and cilostazol had a reduction in the amount of assistance they needed with everyday living tasks, a reduction in cognitive impairment and positive impacts on mood and quality of life. Isosorbide mononitrate alone reduced recurrent stroke, cognitive impairment and improved quality of life; cilostazol alone reduced the need for daily assistance.

“There appeared to be some potential benefits that will need to be confirmed in a larger phase 3 trial,” Wardlaw said. “We saw good hints of efficacy, particularly for isosorbide mononitrate on reducing recurrent stroke and cognitive impairment, and we also found that both medications together seemed to work synergistically, rather than counteracting any benefit. This is very encouraging since no study has previously found any medications that positively affect cognitive impairment in small vessel disease strokes. So, we cautiously hope that these medications may have wider implications for other types of small vessel disease.”

The study has some limitations, including that it was relatively small at 363 patients and not designed to measure efficacy, thus the results showing effectiveness should be interpreted cautiously. The trial was open label, meaning participants and clinicians were aware of which medication/s and doses they were taking; however, the follow-up staff for the study were unaware of which treatment the patients were assigned. Additionally, the investigators did not collect data on race or ethnicity, and many ethnic groups were suspected to be underrepresented.

Study co-lead author is Philip M. Bath, D.Sc., FAHA, UK Stroke Association Professor of Medicine at the University of Nottingham. The list of authors’ disclosures is available in the abstract.

The study was funded primarily by the British Heart Foundation, with support from the UK Alzheimer’s Society, the U.K. Dementia Research Institute, the Stroke Association, the Fondation Leducq, NHS Research Scotland and the U.K. National Institutes of Health Research Clinical Research Networks. The work was conducted by the University of Edinburgh and the University of Nottingham.

Statements and conclusions of studies that are presented at the American Heart Association’s scientific meetings are solely those of the study authors and do not necessarily reflect the Association’s policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association’s scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association’s overall financial information are available here.

Additional Resources:

• Multimedia is available on the right column of release link https://newsroom.heart.org/news/two-cardiovascular-medicines-were-well-tolerated-for-small-vessel-stroke?preview=517678de4cc8e0163d68d15cafafce57
• AHA health information: Types of Heart Medications
• AHA News story: Having ideal heart health may lessen the risk for brain vessel disease (Aug. 2022)
• Research article published in the Journal of the American Heart Association: Small‐Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need, and Future Directions (Feb. 2019)
• For more news at ASA International Stroke Conference 2022, follow us on Twitter @HeartNews #ISC23.

The American Stroke Association’s International Stroke Conference (ISC) is the world’s premier meeting dedicated to the science and treatment of cerebrovascular disease. ISC 2023 will be held in person in Dallas and virtually, Feb. 8-10, 2023. The three-day conference will feature more than a thousand compelling presentations in categories that emphasize basic, clinical and translational sciences as research evolves toward a better understanding of stroke pathophysiology with the goal of developing more effective therapies. Engage in the International Stroke Conference on social media via #ISC23.

About the American Stroke Association

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Prevalence of, and risk factors for, cognitive impairment in lacunar stroke

 Are you that fucking clueless that you think telling us risks rather than providing solutions that prevent those risks is of any use at all to survivors recovery? And your mentors and senior researchers are also that clueless? No wonder stroke never gets solved. We have blithering idiots in stroke.

Prevalence of, and risk factors for, cognitive impairment in lacunar stroke

Show all authors

Laura Ohlmeier, Stefania Nannoni, Claudia Pallucca, ...

First Published January 5, 2022 Research Article 

https://doi.org/10.1177/17474930211064965

Article information

Abstract

Background:

Small vessel disease (SVD) is associated with vascular cognitive impairment (VCI) but why VCI occurs in some, but not other patients, is uncertain. We determined the prevalence of, and risk factors for, VCI in a large cohort of patients with lacunar stroke.

Methods:

Participants with magnetic resonance imaging (MRI)-confirmed lacunar stroke were recruited in the multicenter DNA Lacunar 2 study and compared with healthy controls. A logistic regression model was used to determine which vascular risk factors and MRI parameters were independent predictors of VCI, assessed using the Brief Memory and Executive Test (BMET).

Results:

A total of 912 lacunar stroke patients and 425 controls were included, with mean (SD) age of 64.6 (12.26) and 64.7 (12.29) years, respectively. VCI was detected in 38.8% lacunar patients and 13.4% controls. In a logistic regression model, diabetes mellitus (odds ratio (OR) = 1.98 (95% confidence interval (CI) = 1.40–2.80), p < 0.001) and higher body mass index (BMI) (OR = 1.03 (95% CI = 1.00–1.05), p = 0.029) were independently associated with increased risk of VCI, and years of full-time education with lower risk (OR = 0.92 (95% CI = 0.86–0.99), p = 0.018). When entering both lacune count and white matter hyperintensity (WMH) in the same logistic regression model, only WMH grade was significantly associated with VCI (OR = 1.46 (95% CI = 1.24–1.72), p < 0.001).

Conclusion:

VCI is common in lacunar stroke patients, affecting almost 40%. This prevalence suggests that it should be routinely screened for in clinical practice. Risk factors for VCI in patients with lacunar stroke include diabetes mellitus, depressive symptoms, higher BMI, and WMH severity, while education is protective.

Keywords

Vascular cognitive impairment, small vessel disease, lacunar stroke, white matter hyperintensities

Introduction

Lacunar stroke, usually caused by cerebral small vessel disease (SVD), accounts for a quarter of all ischemic strokes. SVD is characterized radiologically by lacunar infarcts, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and enlarged perivascular spaces.¹ SVD is the most common pathology underlying vascular cognitive impairment (VCI) and vascular dementia.¹

VCI is characterized by executive dysfunction and slowing of information processing speed while episodic memory and orientation in space, time, and person are relatively preserved.² Simple cognitive screening batteries commonly used in clinical practice, such as the Mini-Mental State Examination (MMSE), focus primarily on deficits in orientation and episodic memory, and are less sensitive to the cognitive profile in SVD.^2,3 When tests more sensitive to executive function and processing speed are used, such as the Brief Memory and Executive Test (BMET), a higher prevalence of cognitive impairment is detected in patients with SVD.²

Cardiovascular risk factors, particularly hypertension and diabetes, increase the risk of stroke⁴ and are associated with post-stroke dementia and VCI.⁵ However, most studies include all stroke subtypes, and less data are available specifically on lacunar stroke. Apathy, a decline in goal-directed behavior, which is common in SVD, has been associated with both the degree of white matter damage and dementia in SVD.⁶ Previous studies have reported associations between VCI and the range and severity of magnetic resonance imaging (MRI) markers, such as WMH, lacunar infarcts, and CMB.⁷ Furthermore, the pathology underlying SVD may be heterogeneous and it has been suggested that there are two major pathological subtypes⁸: focal atheroma resulting in larger isolated lacunar infarcts (ILIs) and more diffuse arterial disease associated with multiple smaller lacunar infarcts. More recent studies suggest that a similar distinction can be made on MRI with patients with single lacunar infarcts, those with multiple lacunar infarcts (MLI) and with confluent WMH having distinct risk factor profiles.⁹

Most previous studies have been small, and many have used computed tomography (CT)-based phenotyping, which is less accurate in the diagnosis of lacunar stroke. Furthermore, cognitive tests sensitive to the deficit seen in SVD were not always used. In addition, whether the cognitive profile differs for the different subtypes of VCI is uncertain.

In a large prospective multicenter cohort of almost 1000 patients with MRI-confirmed lacunar stroke, we determined the prevalence of VCI measured using the BMET. We further determined risk factors associated with VCI, including cardiovascular and lifestyle risk factors, as well as MRI features.

 

Lacunar stroke: mechanisms and therapeutic implications

I got nothing out of this, either good or bad.

 Lacunar stroke: mechanisms and therapeutic implications

1. http://orcid.org/0000-0003-0031-1004Shadi Yaghi1,
2. http://orcid.org/0000-0003-2998-8481Eytan Raz2,
3. Dixon Yang2,3,
4. Shawna Cutting1,
5. Brian Mac Grory4,
6. Mitchell SV Elkind5,
7. http://orcid.org/0000-0001-8178-8597Adam de Havenon6

1. Correspondence to Dr Shadi Yaghi, Department of Neurology, Brown University Warren Alpert Medical School, Providence, RI 02903, USA; shadiyaghi@yahoo.com

Abstract

Lacunar stroke is a marker of cerebral small vessel disease and accounts for up to 25% of ischaemic stroke. In this narrative review, we provide an overview of potential lacunar stroke mechanisms and discuss therapeutic implications based on the underlying mechanism. For this paper, we reviewed the literature from important studies (randomised trials, exploratory comparative studies and case series) on lacunar stroke patients with a focus on more recent studies highlighting mechanisms and stroke prevention strategies in patients with lacunar stroke. These studies suggest that lacunar stroke is a heterogeneous disease with various mechanisms, including most commonly lipohyalinosis and less commonly atheromatous disease and cardioembolism, highlighting the importance of a careful review of brain and neurovascular imaging, a cardiac and systemic evaluation. A better understanding of pathomechanisms of neurological deterioration may lead to investigating the utility of novel treatment strategies and optimisation of short-term antithrombotic treatment strategies to reduce the risk of neurological deterioration and prevent long-term disability in patients with lacunar stroke.

http://dx.doi.org/10.1136/jnnp-2021-326308

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Introduction

Lacunar stroke is a marker of cerebral small vessel disease1 and accounts for up to 25% of ischaemic stroke. The word lacunar comes from Latin for ‘lacuna’ meaning hole, and it is used to describe a small focus of encephalomalacia containing CSF, which is the end result of liquefactive necrosis. Lacunar stroke is defined as a subcortical infarct measuring less than 20 mm in diameter, caused by occlusion of a perforator of an intracranial artery.1 In this narrative review, we aim to provide an overview of potential lacunar stroke mechanisms and diagnostic approaches, and discuss therapeutic implications targeting the underlying mechanism.

Background

The incidence of lacunar stroke varies based on the population studied from 25 to 50 per 100 000 people,2 3 comprising 15%–25% of ischaemic stroke.2–4 These numbers, however, have been declining over time, likely due to better control of vascular risk factors such as hypertension.5

Lacunar stroke shares risk factors with other stroke subtypes, namely hypertension, diabetes, advanced age, cigarette smoking and hyperlipidaemia.6 7 While studies have shown that the overall prevalence of these risk factors is similar between lacunar stroke and other stroke subtypes,8 some studies suggest that smoking, hypertension and diabetes are particularly important risk factors for lacunar stroke3 7 and that these risk factors may be more prevalent in patients with lacunar stroke.9 Among these risk factors, hypertension is most common in patients with lacunar stroke (68%), followed by diabetes (30%).3 7 9 These studies were performed when the control of risk factors, particularly hypertension, was less aggressive and more recent studies suggest that risk factors for lacunar stroke may be similar to those of other subtypes.10

In addition to conventional risk factors, rare genetic conditions, such as Cerebral Autosomal Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) can cause lacunar stroke.11 These typically have other accompanying manifestations, including a positive family history, and the diagnosis is made by clinical suspicion and confirmed by genetic testing (table 1).11