American Heart Association

Monthly Archives: December 2015

Clinical characteristics of dorsal medullary infarction

Russell Mitesh Cerejo, MD 

Lee SU, Park SH, Park JJ, Kim HJ, Han MK, Bae HJ, and Kim JS. Dorsal Medullary Infarction: Distinct Syndrome of Isolated Central Vestibulopathy. Stroke. 2015  

The authors Sun-Uk Lee et al, identified 18 patients with dorsal medullary infarcts amongst 172 patients presenting with medullary infarction. Their results can be summarized as follows: 

1) Lesions restricted to the dorsal portion of the medulla may present isolated acute vestibular syndrome.
· Vertigo or unsteadiness (n=15), and was associated with tinnitus the ipsilesional (n=2) or contralesional ear (n=1). 

2) Almost all the patients with dorsal medullary infarctions show findings of central vestibulopathy according to the affected neural structures.
· Direction-changing Gaze Evoked Nystagmus (n=12)
· Negative Head Impuse Test (n=8)
· Skew deviation (n=7)
· Head Shaking Nystagmus in the opposite direction of Spontanous Nystagmus (n=3)
· Perverted Head Shaking Nystagmus (n=3)
· Disjunctive torsional nystagmus (n=2)  

3) Brain imaging including DWI may not detect DMI in about a half of the patients at initial presentation with AVS.
· Negative MRI in 11/18 (10 with 1.5 and one with 3.0-T MRIs) within 10 days of symptom onset (median=one day, IQR=0-3 days) 

 4) Patients with DMI usually show neurological deterioration during the acute phase, but long-term prognosis is excellent.  
5) Most patients had comorbid vascular risk factors and about a half of them had a stroke etiology other than small artery disease.
· Small artery disease n=10
· Large artery disease n = 7
· Vertebral dissection n = 1 

It is important for physicians to recognize symptoms of dorsal medullary infarction as they can often be subtle. The most challenging presentation will be that of isolated vestibular symptoms, highlighting the importance of obtaining a through history for risk factors and examination.  
Schematic illustration of the neural structures involved in patients with dorsal medullary infarction. AN=abducens nucleus; HN=hypoglossal nucleus;

ICP=inferior cerebellar peduncle; IVN=inferior vestibular nucleus; LVN=lateral vestibular nucleus; MLF=medial longitudinal fasciculus; MVN=medial vestibular nucleus; NPH=nucleus prepositus hypoglossi

By |December 31st, 2015|clinical|0 Comments

The feasibility of central adjudication of modified Rankin scale

Peggy Nguyen, MD

López-Cancio E, Salvat M, Cerdà N, Jiménez M, Codas J, Llull L, et al. Phone and Video-Based Modalities of Central Blinded Adjudication of Modified Rankin Scores in an Endovascular Stroke Trial. Stroke. 2015

The modified Rankin scale (mRS) is a standard measure of outcome used in stroke research, but interrater variability exists and unlike imaging markers in which central adjudication is often used, central adjudication of the mRS has not been validated. This can be problematic for studies in which local adjudication of the mRS may lead to observer bias. Video based central adjudication can help with the problem of observer bias and a previous study showed good agreement between central and local evaluation of mRS. In order to better address this, a secondary analysis of the REVASCAT study was completed to look at the feasibility of central mRS adjudication and to compare phone versus video-based central adjudication against the outcome standard of 24-hour infarct volume on neuroimaging.

Patients were assigned a 90-day mRS both locally using a structured interview in a face-to-face visit by an mRS-certified neurologist not involved in the patient’s management as well as centrally. The central adjudication of the mRS was done initially by an external mRS-certified nurse by telephone call using a structured interview, but due to discordance of local and central scores, was changed to a video adjudication method by a single external, mRS-certified neurologist. Significantly, the authors found:

  • Central adjudication, including video adjudication, was feasible; patient information remained secure, video protocol was brief, and the laptop used for video-taping was portable.
  • The inter-rater agreement between local and central assessors was higher when the central assessment was done by video, with 62.5% concordance when central assessment was done by phone compared to 86.8% concordance when central assessment was done by video. In a subset of 55 patients who received both modalities of central adjudication, the agreement was 67.3%, with a wider range of assigned mRS by the phone assessor compared to the video assessor in comparison to the local adjudicator.

The majority of local face-to-face interviews were rated by a central video evaluator as reliable (71.7%), but 10.4% were rated as poor and 17.9% as acceptable. The higher the quality of face-to-face interview, the better the agreement between video based and local assessment.

What does this mean for clinical studies? This does support the feasibility of central adjudication of the mRS using video-taped recordings, which can have a significant impact on the way stroke research is done. Neuroimaging is easily assessed centrally by blinded investigators, but imaging markers do not necessarily correlate with quality of life, which is a much more clinically significant endpoint for both patients and physicians.

By |December 30th, 2015|treatment|0 Comments

Does stroke cause reactive amyloid-beta deposition in nondemented patients? Results from a 11C-PiB-PET longitudinal cohort

Danny R. Rose, Jr., MD

Sahathevan R, Linden T, Villemagne VL, Churilov L, Ly JV, Rowe C, et al. Positron Emission Tomographic Imaging in Stroke: Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke. Stroke. 2015

The relationship between cerebrovascular disease, cognition and amyloid-beta (Aβ) deposition as occurs in Alzheimer’s Disease (AD) and related disorders has been a topic of much debate and research. Cardiovascular risk factors such as hypertension and diabetes independently increase the risk of vascular cognitive impairment (VCI) and AD, and histopathologic analysis shows considerable overlap between the pathologic features of the two conditions. Despite this, studies in human subjects that attempt to establish a causal relationship between ischemia and Aβ deposition have been mostly negative. Sahathevan et al. sought to investigate the relationship between ischemia and Aβ deposition both in the acute setting and over time. In a single-center cohort of patients with acute ischemic stroke, they quantitatively assessed Aβ using amyloid PET imaging (11C-PiB-PET) around the time of their event and again several months later.


Forty-eight patients who presented with a first-ever acute ischemic stroke were scanned within 40 days of the event with 11C-PiB-PET and MRI for anatomic co-registration. Patients with previous intracerebral hemorrhage, head trauma, brain surgery, brain tumor and known neurodegenerative disorders were excluded. Baseline data included demographics, vascular risk factor profiles, stroke topography and the presence or absence of hemorrhagic transformation, white matter lesions and carotid stenosis. Standard uptake value ratios (SUVR) on amyloid PET imaging were generated for the infarct and peri-infarct regions and compared to a mirrored reference region in the contralesional hemisphere. Ipsilesional and contralesional hemisphere SUVR values were also generated. A cut-off of SUVR=1.40 was used to identify high versus low uptake based on prior studies by the authors. Assessment of hemorrhagic transformation on MRI (which was found to be correlated to increased SUVR in a previous study by the authors) was performed for inclusion as a confounding variable. The presence of white matter lesions based on Fazekas scores and presence of carotid disease were used as surrogate markers to investigate the potential effect of chronic ischemia as another confounding variable.

Of the initial 48 patients, 27 did not return for repeat scans due to medical or other reasons. Baseline demographics were not significantly different between those who did and did not have a second amyloid PET scan, except that a higher percentage of patients with hypertension declined to return. The median time to second scan was 222 days.

The SUVR of the infarct areas were >1.4 in 57.9% patients at baseline, compared to 51.1% in the reference region. The median difference (0.07) was not significant (p=0.452). The median difference in SUVR of the infarct zone at time of follow-up imaging was -0.08 (p=0.04), suggesting a significant decrease over time. Similarly, nonsignificantly higher values in the affected region coupled with a statistically significant decrease on follow-up imaging were found in the peri-infarct zone as well as the stroke-specific hemisphere. There was no effect of hemorrhagic transformation or carotid disease. The presence of periventricular WML did affect the decrease in hemisphere-specific SUVR on follow-up imaging (p=0.03), but this effect was not found in the infarct or peri-infarct regions. Deep WML did not affect any of the studied regions.

This study provides valuable insights into the complex pathology behind Aβ deposition in the brain despite the high attrition rate, low number of patients, and variation in time between scans. The authors’ hypothesis of reactive Aβ deposition based on their prior work with a smaller group of subjects was not supported, and the significant reduction in 11C-PiB-PET accumulation over time across all studied regions suggests the increased uptake around the time of the ischemic event is due to a transient increase in blood brain barrier permeability that occurs following an acute stroke. Further study with larger cohorts and standardized, serial PET imaging would likely provide more clarity in this regard.

The lack of association with carotid stenosis contrasts with a smaller previous study of demented patients with unilateral carotid stenosis that showed increased uptake in the hemisphere distal to the stenosis. That observation is of particular interest as it suggests that ischemia and cerebrovascular disease may play a modulating role in Aβ pathology that is more pronounced in demented patients who likely have other predisposing factors towards Aβ deposition. An extended longitudinal study using amyloid PET imaging to compare the evolution of Aβ uptake over time in patients with stroke who went on to develop AD versus those who did not could be helpful, as well as examining the role of APoE allele status in a similarly designed study.

Poor collateral status is associated with poor clinical outcomes

Jay Shah, MD

van den Wijngaard IR, Boiten J, Holswilder G, Algra A, Dippel DWJ, Velthuis BK, et al. Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke. Stroke. 2015

Despite recent endovascular trials demonstrating improved outcomes, rate of functional dependence or death at 3 months following anterior circulation infarct secondary to proximal occlusion remains high. Clinical factors predicting clinical outcome include age, baseline stroke scale, and blood pressure. A radiological factor that has been shown to positively correlate with clinical outcome is collateral status. While digital subtraction angiography is considered the gold standard, this method is unfeasible in the acute setting. A non-invasive modality is dynamic-CTA which provides time-resolved images of arterial, parenchymal, and venous phases. In this study, the authors investigated the value of collateral status in predicting clinical outcomes. 

Patients were retrospectively selected from the Dutch Acute Stroke Trial (DUST) and the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN). In total, 70 patients with proximal middle cerebral artery occlusion were selected in whom dynamic CTA was obtained. CTA was scored on a 0-3 scale, 3 corresponding to complete collateral filling of the occluded territory. Speed of collateral filling was also measured and dichotomized to fast versus slow filling based on filling of the asymptomatic hemisphere.

Of the 70 patients, only 17 patients underwent endovascular treatment. At 3 months, 60 patients had either dead or had poor clinical outcome, as defined as a modified rankin score of greater than three. Poor clinical outcome was strongly related to poor arterial filling on dynamic CTA. Risk of poor outcome decreased with increasing collateral score. Speed of filling did not have a strong correlation to clinical outcome.

This study suggests that dynamic CTA can reliably assess collateral status and that collateral status is positively correlated with clinical outcome. This study, however, was limited by relatively low number of patients. Furthermore, this study was not powered to assess affect of collateral status on treatment types. Therefore, conclusions regarding patient selection for acute treatment would be premature. Further studies are needed to determine clinical utility of obtaining collateral status in the acute setting. For example, a patient with a proximal anterior circulation occlusion with poor collaterals who presents within the appropriate time frame should still be offered endovascular therapy. One potential utility of obtaining collateral status, as supported by this study, could be to aid in prognostication for patients and families.

IV tPA has an important role even in the presence of endovascular therapy.

Russell Mitesh Cerejo, MD

Desilles JP, Loyau S, Syvannarath V, Gonzalez-Valcarcel J, Cantier M, Louedec L, et al. Alteplase Reduces Downstream Microvascular Thrombosis and Improves the Benefit of Large Artery Recanalization in Stroke. Stroke. 2015

Dr. Jean-Philippe Desilles and colleagues studied the effects of IV tPA in downstream microvascular thrombosis. In their animal model they used rats with middle cerebral artery (MCA) occlusion for 60 minutes and then randomized them to IV tPA vs saline. They used Intravital fluorescence microscopy to visualize the circulating blood cells and fibrinogen. They also assessed for infarct volumes and neurological deficit. After sacrifice of the rats, they also assessed for patency of the microvasculature and plasma fibrinogen levels.

The authors found that immediately after occlusion of the MCA, there was early and pronounced adhesion of leukocytes and platelets that occurred almost exclusively in the venous compartment and persisted up to 1 hour post recanalization. There also was microthrombosis characterized by intraluminal deposition of fibrinogen developed in post-capillary micro vessels at sites of leukocyte and platelet accumulation, which caused complete cessation of blood flow.

 
Intravenous alteplase injection at 10 mg/kg 30 minutes after initiating MCA occlusion significantly reduced infarct size and also improved neurological deficits, evaluated 24 hours. In a subgroup of rats that were sacrificed before recanalization of the MCA occlusion showed that early administration of alteplase improves microvascular patency and stroke outcome indicating that alteplase exerts beneficial effects independently of its action on proximal arterial recanalization. Alteplase fibrinolytic activity induces a rapid and profound hypofibrinogenemia that prevents platelet aggregation and promotes disaggregation of freshly formed platelet aggregates.

These finding suggest that the use of IV alteplase treatment in eligible patients supplement endovascular therapy to improve the benefit of large artery recanalization, through targeting of downstream micro vascular thrombosis.

As in adults, TIA heralds stroke in Children

Alexander E. Merkler, MD

Lehman LL, Watson CG, Kapur K, Danehy AR, and Rivkin MJ. Predictors of Stroke After Transient Ischemic Attack in Children. Stroke. 2015

Pediatric stroke is a leading cause of death and disability in children. In adults, stroke occurs in 10-15% of adults within 3 months of transient ischemic attack (TIA), but little is known about risk of stroke after TIA in children. In this manuscript, Dr. Lehman et al evaluate predictors of stroke after TIA in children.

63 children were identified as having a TIA at Boston Children’s Hospital. TIA was defined using the time-based definition: a focal neurological deficit that resolved within 24 hours. All patients were required to have an MRI within 3 months of TIA. Similar to adults, almost 80% of patients had motor symptoms. Headache accompanied TIA in 54% of children, but only 10% of patients carried a diagnosis of migraine.

After a median follow-up of 4.5 years, 10/63 children (16%) developed MRI evidence of stroke, 4 (6%) of whom had imaging evidence of stroke at the time of TIA, and 8 (13%) of whom developed new imaging evidence of ischemic injury not seen on the MRI done at the time of TIA.

Independent predictors for stroke after TIA included female sex (OR 11.3, 95% CI, 1.3-98.7), cerebral arteriopathy (OR 24.5, 95% CI, 4.0-149.8), and presence of autoimmune disorders (OR 26.5, 95% CI, 3.6-191.6).

Limitations included 1) small number of patients and therefore wide confidence intervals; 2) retrospective design; 3) use of a time-based definition of TIA thereby likely included cerebrovascular mimics such as migraine.

Overall, similar to adults, children with TIA seem to have a significant risk of developing a stroke. Risk factors for stroke after TIA include female sex, cerebral arteriopathy, and presence of an autoimmune disorder. Further research will be necessary to confirm these findings and help prevent the development of stroke in the pediatric population.

By |December 23rd, 2015|prognosis|0 Comments

Randomized trial shows telephone-based comprehensive caregiver education and support can help mood and quality of life for caregivers of stroke survivors

Danny R. Rose, Jr., MD

Bakas T, Austin JK, Habermann B, Jessup NM, McLennon SM, Mitchell PH, et al. Telephone Assessment and Skill-Building Kit for Stroke Caregivers: A Randomized Controlled Clinical Trial. Stroke. 2015

The myriad of challenges that caregivers of stroke survivors face is an under-recognized consequence of stroke that has significant implications on quality of life for both the caregiver and patient. A 2014 American Heart Association scientific statement reviewed the available scientific literature regarding caregiver interventions and recommended individualized programs that combine skill-building with psycho-educational strategies. The variation in studies cited in that report reflect the current lack of evidence with respect to the most effective and feasible approach to implement such an intervention. Bakas et al. sought to investigate the efficacy of the revised Telephone Assessment and Skill-Building Kit (TASK II, a multifaceted caregiver intervention program) by conducting a randomized controlled clinical trial comparing TASK II to a more traditional program, Support and Referral (ISR) strategy, to determine if a more comprehensive intervention improved caregivers’ mood and quality of life. 

A total of 254 stroke caregivers were randomized to either the TASK II group (n=123) or to the ISR comparison group (n=131). Caregivers were deemed appropriate for inclusion if they were the primary caregiver, 21 years of age or older, anticipated providing care for at least one year and were able to participate in the telephone calls and interviews. Caregivers and stroke survivors were excluded if they had severe cognitive issues, severe mental illness or had been hospitalized for alcohol or drug abuse. Demographics between the two groups were similar. Caregivers were primarily women (78.0%, TASK II; 78.6% ISR), about half spouses (48.4%, TASK II; 46.6%, ISR), predominantly White (70.7%, TASK II; 72.1%, ISR), and ranged in age from 22 to 87 years.

Both groups received an information pamphlet from the American Heart Association. Caregivers randomized to the TASK II intervention group also received a resource guide including a checklist addressing caregiver needs regarding finding information, providing physical and instrumental care as well as managing the survivor’s emotions and behaviors. The resource guide also included skill building information for screening for depressive symptoms, maintaining realistic expectations, communicating with healthcare providers as well as stress management for the caregiver and stroke survivor. Both groups received 8 weekly calls from a nurse with a booster call at 12 weeks. Calls to the caregivers in the TASK II group focused on identifying and prioritizing their needs and concerns and using the resources in the resource guide with skill-building strategies. Calls to caregivers in the ISR group focused on providing support through active listening strategies. Baseline data were collected within 8 weeks after the stroke survivor was discharged, and follow-up data were collected at 8 weeks (post-intervention), 12 weeks and at 24 and 52 weeks. Caregiver outcomes were assessed using validated questionnaires on depressive symptoms (Patient Health Questionnaire Depressive Symptom Scale, PHQ-9), changes in social functioning, subjective well-being, and physical health (Bakas Caregiving Outcomes Scale, BCOS), and Unhealthy Days, measured by summing two items asking caregivers to estimate the number of days in the past 30 days that their own physical and/or mental health had been poor.

At baseline, approximately half of the caregivers in each group reported mild to severe depressive symptoms (defined as PHQ-9 ≥ 5). For that subgroup, caregivers in the TASK II group reported a greater reduction in depressive symptoms from baseline to 8 weeks compared to the ISR group (mean difference -2.6, p= 0.013) The effect was also found when comparing baseline to 24 weeks (mean difference -1.9, p=0.041) and baseline to 52 weeks (mean difference -3.0, p=0.041). This subgroup also had a significant improvement in life changes compared to ISR participants from baseline to 12 weeks. This difference was not present for the cohort as a whole for either endpoint. Caregivers in the TASK II group also had a greater reduction in unhealthy days from baseline to 8 weeks compared to the ISR group (mean difference -2.9, p=0.025).

This study represents an important step in the continued effort to design and revise evidence-based programs to provide targeted caretaker support. Based on this study, it appears that caretakers with baseline depressive symptoms are a particularly vulnerable subset that tend to benefit from caregiver interventions in general and do better with interventions targeted at identifying needs and building problem solving skills. It is also worth noting that this represents the first telephone-based intervention showing durable results up to one year for any group of caretakers, and is much more feasible compared to interventions focusing on in-person counseling. Further research on a larger scale resulting from the incorporation of this and similar caregiver well-being intervention strategies into existing stroke systems of care will likely continue to improve our understanding of the most efficient and effective way to provide targeted interventions to improve caretaker well-being
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By |December 22nd, 2015|health care, policy|0 Comments

Recurrent ischemic stroke risk in children

Neal S. Parikh, MD

Fullerton HJ, Wintermark M, Hills NK, Dowling MM, Tan M, Rafay MF, et al. Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study. Stroke. 2015

Citing a paucity of contemporary pediatric stroke recurrence risk data, Fullerton and colleagues conducted a prospective study to measure recurrent stroke rates and risk factors for recurrent strokes in children.

Patients were enrolled from 2010 to 2014 from 37 centers across 9 countries for the Vascular effects of Infection in Pediatrics (VIPS) protocol. Strokes were classified as having definite, possible or no arteriopathy and then further subdivided into transient cerebral arteriopathy, arterial dissection, moyamoya, vasculitis, or other. Strokes without arteriopathy were classified as idiopathic, cardioembolic or other. The researchers also collected data regarding infections in the 3 weeks prior to the index stroke and patients’ vaccination statuses.

355 children were enrolled and followed over a median of 2 years. 87% were treated with antithrombotic medications. There were 42 recurrent strokes, all ischemic, at a median of 23 days from index stroke. 6.8% had 1-month recurrence; 12% had 1-year recurrence.

The only predictor of recurrent stroke was definite arteriopathy, which increased the hazard of recurrence by five-fold compared to idiopathic index stroke. 21% of children with index stroke due to definite arteriopathy experienced a recurrent stroke. The highest recurrence rate was for children with moyoamoya disease. 75% of recurrent strokes occurred within 12 weeks of index stroke. Of note, though these authors previously showed recent infection and unvaccinated status to be associated with incident stroke, these variables were not associated with recurrent stroke risk.

The high stroke recurrence rate in children with arteriopathy is remarkable. As the authors conclude, arteriopathy – particularly forms in children such as transient cerebral arteriopathy and moyamoya disease – may have unique pathophysiologic underpinnings and therefore treatments.

CT perfusion based selection inadequate for stratifying patients for intra-arterial treatment

Peggy Nguyen, MD 

Borst J, Berkhemer OA, Roos YBWEM, van Bavel E, van Zwam WH, van Oostenbrugge RJ, et al. Value of Computed Tomographic Perfusion–Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment. Stroke. 2015 
 

The current treatment of acute ischemic stroke is largely dependent on the timing of presentation from ictus; that is, thrombolytics up to 4.5 hours and thrombectomy up to 6 hours from onset, but many patients continue to present outside of the window for intervention. The use of advanced imaging modalities for markers to stratify patients who may benefit is an area of enormous interest. Here, the authors looked at a subset of 175 patients in the MR CLEAN study who underwent CT perfusion with the goal of evaluating the relationship between CTP deprived parameters and functional outcome, investigating whether the efficacy of intraarterial treatment (IAT) on outcome was modified by the CTP derived parameters, and investigating the effect of CTP mismatch selection on the efficacy of IAT.
The authors did find a significant association between both CTP-derived ischemic core volume and percentage ischemic core and functional outcome, but not penumbra volume, indicative of a poorer functional outcome with larger ischemic core. However, there was no interaction between CTP derived parameters (ischemic core volume, penumbra volume, and percentage ischemic core) and treatment effect, indicating that the efficacy of IAT was independent of CTP parameters.

CTP mismatch, defined per criterion used in EXTEND-IA as an ischemic core < 70 mL and a penumbra of at least 10 mL and 20% larger than the ischemic core, was present in 102/175 patients. Patients with mismatch present were more likely to have a higher NIHSS and presence of an ICA terminus occlusion. There was no significant interaction between mismatch and treatment effect on the mRS scale endpoint nor on the dichotomized endpoints of mRS. Patients with a large ischemic core > 70 mL experienced higher mortality than those with smaller ischemic cores. All patients, despite the volume of ischemic core, had a shift towards better outcome after IAT compared to usual care alone.

This study confirms the benefit of IAT for acute ischemic stroke, even in those with a large CTP ischemic core, shows that larger ischemic core volumes are associated with worse functional outcomes, but found no interaction between treatment effect and CTP core volume nor other CTP derived parameters. The authors point out that CTP appears useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from IAT. Further studies are needed.

Non-disabling DWI negative strokes – Outcomes

Russell Mitesh Cerejo, MD

Makin SDJ, Doubal FN, Dennis MS, and Wardlaw JM. Clinically Confirmed Stroke With Negative Diffusion-Weighted Imaging Magnetic Resonance Imaging: Longitudinal Study of Clinical Outcomes, Stroke Recurrence, and Systematic Review. Stroke. 2015

The authors, in their paper titled “Clinically-confirmed stroke with negative DWI MRI. Long term clinical outcomes, stroke recurrence and systematic review”, raise an important question, if a patient with clinical symptoms of stroke has a negative DWI – MRI does that patient have a better prognosis? To answer this question they performed a prospective observational study over 2 years of patients presenting to a single center with acute non-disabling strokes. They collected initial clinical and imaging characteristics and followed these patients for a year. 

 They enrolled 264 patients of whom nearly one-third had no acute lesion on MRI. DWI-positive patients were more likely to have carotid stenosis, Atrial arrhythmias, higher NIHSS, more White matter hyper intensities and cortical stroke. DWI-negative patients were more likely to have ischemic heart disease or a previous stroke, and be scanned later. After adjustment for age and sex, any embolic source and time to scanning were no longer associated with lesion presence. Of the 198 patients that follow up with a 1-year scan, the patients without an acute ischemic index MRI lesion were just as likely to have persistent symptoms, cognitive impairment, stroke-related disability (mRS≥2), or recurrent stroke/TIA as those who had a DWI-positive index lesion.

They also performed a meta-analysis of prior studies looking at non-disabling strokes and MRI findings and found a similar number of DWI negative strokes in those patients. The study suggests that even in DWI negative patients presenting with acute stroke symptoms, secondary prevention must be pursued as aggressively as in those with DWI-positive stokes.