Presence Of White Matter Disease Research Articles

Health Factors Associated With Development and Severity of Poststroke Dysphagia: An Epidemiological Investigation.

Dysphagia after stroke is common and can impact morbidity and death. The purpose of this population-based study was to determine specific epidemiological and health risk factors that impact development of dysphagia after acute stroke. Ischemic and hemorrhagic stroke cases from 2010 and 2015 were identified via chart review from the GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study), a representative sample of ≈1.3 million adults from southwestern Ohio and northern Kentucky. Dysphagia status was determined on the basis of clinical assessments and necessity for alternative access to nutrition via nasogastric or percutaneous endoscopic gastrostomy tube placement. Comparisons between patients with and without dysphagia were made to determine differences in baseline characteristics and premorbid conditions. Multivariable logistic regression determined factors associated with increased risk of dysphagia. Dysphagia status was ascertained from 4139 cases (1709 with dysphagia). Logistic regression showed that increased age, Black race, higher National Institutes of Health Stroke Scale score at admission, having a hemorrhagic stroke (versus infarct), and right hemispheric stroke increased the risk of developing dysphagia after stroke. Factors associated with reduced risk included history of high cholesterol, lower prestroke modified Rankin Scale score, and white matter disease. This study replicated previous findings of variables associated with dysphagia (older age, worse stroke, right-sided hemorrhagic lesions), whereas other variables identified were without clear biological rationale (eg, Black race, history of high cholesterol, and presence of white matter disease) and should be investigated in future studies to determine biological relevance and potential influence in stroke recovery.

Cognitive Testing During Mild Acute Ischemic Stroke Predicts Long-Term Return to Work

ObjectivesMany survivors of a mild ischemic stroke do not return to work or driving. Cognitive testing is commonly done to assess long-term cognitive impairment after stroke. Inpatient cognitive testing during the acute period of ischemic stroke may also be a predictor for workforce reengagement and functional outcome. Materials and methodsAt our comprehensive stroke center, we prospectively enrolled previously working adults < 65 years old who were diagnosed with first-ever ischemic stroke, had a prestroke modified Rankin Scale (mRS) ≤ 1 and NIHSS ≤ 3. Testing performed within 1 week of stroke included the Montreal Cognitive Assessment (MOCA), Clock Drawing Test (CDT), Trail Making Tests A and B, Backward Digit Span Test, and Hospital Anxiety and Depression Scale (HADS). Other data obtained included age, gender, years of education, occupation, stroke location, stroke laterality, and presence of white matter disease on imaging. Outcome measures assessed at 3 months, 6 months, and 12 months post-stroke included return to work, return to driving, and mRS. In a logistic regression analysis, we performed both univariate and multivariate analyses. Multivariate analysis was completed on variables with p-value ≤ 0.05 in the univariate analysis. ResultsOf 39 total stroke patients enrolled and tested (median [IQR] age 55 [46–60] years; 77.5% male; 22.5% female), 36 completed 3-month follow up, of which 58% returned to work, 78% returned to driving, and 72% had mRS of 0–1. In multivariate analysis, a single point increase in the clock drawing task score increased the odds of return to work by 3.79 (95% CI, 1.10–14.14) and return to driving by 6.74 (95% CI, 1.22–37.23) at 3 months. MOCA and HADS were both associated with mRS ≤ 1. MOCA was associated with return to work at 6 months and CDT was associated with return to work at 12 months. ConclusionCognitive testing with CDT and MOCA in the acute period after ischemic stroke may predict common patient goals post stroke, including return to work, driving, and independence. These tools can potentially be used for prognosis and identifying those who may benefit from further interventions.

Abstract P210: Cognitive Testing During Mild Acute Ischemic Stroke Predicts Return to Work, Driving, and Good Functional Outcome at 3 Months

Introduction: Many patients after a mild ischemic stroke (IS) do not return to work or driving. Cognitive testing is commonly done to assess long-term cognitive impairment after IS. However, inpatient cognitive testing during the acute period of mild IS may also be a predictor for workforce reengagement and functional outcome. Methods: At our comprehensive stroke center, we prospectively enrolled previously working adults age &lt;65 years who were diagnosed with first-ever IS, had a prestroke modified Rankin Scale (mRS) ≤1 and NIHSS ≤3. Testing performed within 1 week of IS included the Montreal Cognitive Assessment (MOCA), Clock Drawing Test, Trail Making Tests A and B, Backward Digit Span Test, and Hospital Anxiety and Depression Scale (HADS). Other data obtained included age, gender, years of education, occupation (blue collar or white collar), stroke location (cortical, subcortical, or posterior fossa), stroke laterality, and presence of white matter disease on imaging. Outcome measures assessed at 3 months post stroke included return to work, return to driving, and mRS ≤1. In a logistic regression analysis, we performed both univariate and multivariate analyses. Multivariate analysis was completed on variables p ≤0.05 in the univariate analysis. Results: Of 40 total IS patients enrolled (median [IQR] age 55 [46-60] years; 22.5% female), 36 completed 3-month follow up. 58% returned to work, 78% returned to driving, and 72% had mRS of 0-1 at 3 months. In multivariate analysis, a single point increase in the Clock Drawing Test score increased the odds of return to work by 3.79 (95% CI, 1.10-14.14) and return to driving by 6.74 (95% CI, 1.22-37.23). MOCA and HADS were both associated with mRS ≤1. Conclusion: Clock Drawing Test in the acute period after mild IS may predict early return to work and driving at 3 months. MOCA and HADS may also predict good functional outcome. These tools can potentially be used for prognosis and identifying those who may benefit from further interventions.

In the Kingdom of Triphasic Waves, White Matter Is the Eminence Grise.

Triphasic waves (TWs) have been associated with multiple conditions and adverse outcomes. This study explores the role of white matter disease (WMD) in the generation of TWs when other common causes associated with these discharges are absent. This is a retrospective case series performed at Johns Hopkins Bayview Medical Center from January 2016 to May 2018, which screened for patients with severe WMD, who had TWs on EEG without the presence of commonly cited provoking factors, including (1) hepatic disease; (2) severe uremia over baseline; (3) the drugs cefepime, ifosfamide, lithium, and baclofen; or (4) global hypoxic-ischemic injury. A control population with no WMD or abnormal electrographic findings outside of theta-delta slowing was also identified. Eleven patients were identified. The most common comorbid condition was infection, occurring in 82% of patients. Infections were urinary tract infection (36%), respiratory (27%), and central nervous system (18%). Metabolic abnormalities included glucose aberrations (36%), calcium derangements (18%), and hypernatremia (9%). Structural abnormalities included acute stroke (9%) and chronic central nervous system abscess (9%). All except one patient had one or more structural, metabolic, or infectious abnormalities in addition to WMD. Comorbidities were not statistically different in the control population. This is the first series to demonstrate convincingly the presence of TWs in patients with WMD in the absence of commonly cited risk factors. The authors hypothesize that less recognized risk factors of WMD and mild metabolic or infectious abnormalities may be drivers of TWs. With a growing elderly population, the presence of WMD will increase, and treating physicians need to look beyond the common causes of TWs.

Abstract 135: Examining the Information Loss Between Neuroimages and Neuroimaging Reports for Detection of Silent Brain Infarcts and White Matter Disease Using Artificial Intelligence Technologies

Background: Real world studies of silent brain infarction (SBI) and white matter disease (WMD) are impeded by challenges in cohort identification. Natural language processing (NLP) from imaging reports may facilitate future studies. However, electronic health records can be heterogeneous and the process of interpreting neuroimages and generating reports can vary. Understanding knowledge representation and relationships between neuroimages and imaging reports is crucial for using NLP to facilitate disease management and cohort identification. Methods: A balanced sample of head neuroimages (CT, MRI) of patients &gt;50 years without clinical histories of symptomatic stroke, TIA, or dementia were obtained at Mayo Clinic and Tufts Medical Center. A team of 4 radiology residents performed report interpretation (RI) on 1000 reports according to a standardized protocol for the presence of SBIs, the presence of WMD, and WMD grade. A random subsample of 400 was doubly read for interrater reliability. For benchmarking, a team of 4 neuroradiologists directly reviewed and described findings on a subsample of 182 images, each doubly read. We assessed interrater reliability for direct review (DR) and RI, and agreement between these 2 information sources. An NLP algorithm was developed to review and extract findings from 1000 imaging reports. Results: For DR, interrater reliability was moderate for SBIs and WMD (k = 0.53, 95% CI 0.43-0.64 and k = 0.47, 95% CI 0.33-0.61) and good for WMD grade (Spearman 0.71, p&lt;0.001). For RI, interrater reliability for SBIs, WMD and WMD grade was good (k = 0.88, 95% CI 0.80-0.97; k = 0.98, 95% CI 0.97-1.00; and Spearman = 0.985, p&lt;0.001, respectively). Agreement between DR and RI was good for SBIs (k = 0.77, 95% CI 0.67-0.86) and WMD (k = 0.65, 95% CI 0.54-0.77). Spearman rank correlations comparing WMD grade interpretation DR to RI was 0.60 (p&lt;0.001). In identifying the presence of SBIs and WMDs, the accuracy of the NLP algorithm was 0.991 and 0.994, respectively. Conclusion: For the presence of SBI and WMD, and WMD grade, agreement between RI and DR was similar to agreement between 2 neuroradiologists directly reviewing neuroimages. It is highly feasible to use NLP to identify patients with SBIs and WMDs for clinical studies.

Family History in Young Patients With Stroke

Family history of stroke is an established risk factor for stroke. We evaluated whether family history of stroke predisposed to certain stroke subtypes and whether it differed by sex in young patients with stroke. We used data from the Stroke in Fabry Patients study, a large prospective, hospital-based, screening study for Fabry disease in young patients (aged <55 years) with stroke in whom cardiovascular risk factors and family history of stroke were obtained and detailed stroke subtyping was performed. A family history of stroke was present in 1578 of 4232 transient ischemic attack and ischemic stroke patients (37.3%). Female patients more often had a history of stroke in the maternal lineage (P=0.027) than in the paternal lineage. There was no association with stroke subtype according to Trial of Org 10172 in Acute Stroke Treatment nor with the presence of white matter disease on brain imaging. Patients with dissection less frequently reported a family history of stroke (30.4% versus 36.3%; P=0.018). Patients with a parental history of stroke more commonly had siblings with stroke (3.6% versus 2.6%; P=0.047). Although present in about a third of patients, a family history of stroke is not specifically related to stroke pathogenic subtypes in patients with young stroke. Young women with stroke more often report stroke in the maternal lineage. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

Elevated Levels of Hemoglobin A1c Are Associated With Cerebral White Matter Disease in Patients With Stroke

This study was conducted to investigate the association of cerebral white matter disease (WMD) on MRI with vascular risk factors and laboratory findings in consecutive first acute ischemic stroke patients. Acute ischemic stroke patients underwent MRI ≤24 hours after stroke onset and follow-up on day 2. WMD was scored on fluid attenuated inversion recovery MRI according to the Wahlund score. Vascular risk factors and laboratory parameters were assessed during hospital stay. Univariate and multiple logistic regression analyses were performed. We included 512 patients with first acute ischemic stroke (mean age, 68.5 [SD, 13.2] years; 192 women (37.5%); median National Institutes of Health Stroke Scale on admission, 3 [interquartile range, 1-6]; and median Wahlund score, 4 [interquartile range, 2-9]). WMD was present in 460 (89.8%) patients. In univariate analysis, age, arterial hypertension, reduced estimated glomerular filtration rate, hemoglobin A1c (HbA1c) levels, diabetes mellitus, and female sex were associated with the presence of WMD (P<0.05). In multiple regression analysis, age, arterial hypertension, and elevated levels of HbA1c (P<0.05) remained independently associated with the extent of WMD. Among known risk factors, higher levels of HbA1c were associated with cerebral WMD in stroke patients. This may suggest that chronic disturbance of glycemia measured by HbA1c plays a role in the pathophysiology of WMD. http://www.clinicaltrials.gov. Unique identifier: NCT00715533.

FLAIR Vascular Hyperintensities in Acute ICA and MCA Infarction: A Marker for Mismatch and Stroke Severity?

Background: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. Methods: MR images of 84 patients [median age 73 years (IQR 65–80), 56.0% male, median NIHSS 7 (IQR 3–13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed. Results: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2–7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients. Conclusions: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity.

Microbleeds and the Risk of Recurrent Stroke

We studied the risk of recurrent cerebrovascular events in patients who had a transient ischemic attack or ischemic stroke and who had evidence of microbleeds on MRI. A prospective follow-up study was performed on hospitalized patients who were at least 50 years old with a transient ischemic attack or an ischemic stroke. The presence and number of microbleeds were assessed on gradient echo MRI and the presence of white matter disease on fluid-attenuated inversion recovery imaging using a semiquantitative scale. Patients were followed up by phone every 6 months. End points were intracerebral hemorrhage, ischemic stroke, and unclassified stroke. Cerebral events were adjudicated by 2 independent neurologists blinded to the presence of microbleeds. Cox regression analysis was performed. A total of 487 patients with a mean age of 72 years were followed up for a median of 2.2 years (25th to 75th percentile 1.9 to 2.7 years). Microbleeds were identified in 129 patients (25.6%). Two patients developed intracerebral hemorrhage during follow-up, 32 patients developed recurrent ischemic stroke, and 3 patients had unclassified strokes. Microbleeds were not independent predictors of recurrent stroke (P=0.2) or intracerebral hemorrhage (P=0.43). Lobar microbleeds or combined lobar and deep microbleeds were independently associated with recurrent stroke (P=0.018). In this European cohort, patients with microbleeds who have had cerebral ischemia have a higher risk of developing new ischemic strokes than of intracerebral hemorrhage. Lobar microbleeds or combined lobar and deep microbleeds might be independent predictors of recurrent stroke.

Morbilidad a los dos años de edad en niños con un peso al nacimiento menor de 1.500 g

To determine morbidity at 2 years' corrected age in a cohort of neonates with a birth weight of less than 1,500 g born in 1999-2000 in a tertiary hospital in the Autonomous Community of Madrid. An observational longitudinal follow-up study was performed in a cohort of 213 infants with a birth weight of < 1,500 g. Of these, 188 (87%) completed the 2-year follow-up. Various types of neurosensorial disability were studied, paying special attention to the main impairments: vision, hearing and motor impairment, and low development quotient. Among the patients initially included in the study, 87% completed the follow-up; 17.1% had one or more major sequela. We found one case (0.4%) of bilateral neurosensorial deafness and one case of bilateral blindness. At the age of 2 years, 5.8 % (11/188) had cerebral palsy, 14.9% had a development quotient below 85 and 18% had not reached the 3rd percentile for weight. Factors of poor neurological prognosis were subnormal head size at the age of 2 years and white matter disease (including persistent intraparenchymal periventricular echodensity and ventriculomegaly or irregular shape) as ultrasound findings. Less than a fifth of the very low birth weight infants presented severe sequelae at 2 years of follow-up. Factors of poor neurological prognosis were subnormal head size at 2 years and the presence of white matter disease on ultrasonography. The findings on growth and development were worrying, since 18 % of the patients had not reached the 3rd percentile for weight at 2 years' corrected age.

White Matter Disease in Magnetic Resonance Imaging Predicts Cerebral Complications After Coronary Artery Bypass Grafting

The aim of the present study was to assess neurologic and neuropsychologic complications in 104 patients randomized to coronary artery bypass grafting or spinal cord stimulation. An additional objective of the study was to assess whether preoperative white matter disease might predict cerebral complications, as previous studies have shown that there is a relationship between white matter disease and neuropsychologic decline after coronary artery bypass grafting. The patients were subjected to neurologic examination before and six months after intervention. The patients underwent a cerebral magnetic resonance imaging before intervention and the presence of white matter disease was related to development of cerebral complications. More patients in the bypass group than in the spinal cord stimulation group developed focal cerebral ischemia (p < 0.05) and astheno-emotional disorder (p < 0.001). More patients with white matter disease undergoing bypass were affected by focal cerebral ischemia (p < 0.01) and astheno-emotional disorder (p < 0.001) after the intervention compared to patients with white matter disease undergoing spinal cord stimulation. In patients with no white matter disease there were no differences between the bypass group and spinal cord stimulation group with regard to cerebral complications. Patients undergoing bypass had more neurologic and neuropsychologic complications than patients undergoing spinal cord stimulation. Furthermore, patients with white matter disease were affected by cerebral complications in a higher extent after bypass than after spinal cord stimulation. Thus, preoperative assessment of white matter disease before undergoing coronary artery bypass grafting might predict the patient's risk of developing cerebral injury.

Intrathecal release of pro- and anti-inflammatory cytokines during stroke.

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

Neuropathology of White Matter Changes in Alzheimer’s Disease and Vascular Dementia

Morphological white matter changes were investigated in clinically and neuropathologically diagnosed cases of Alzheimer’s disease (AD; 60 cases) and vascular dementia (VaD; 40 cases). In 33 of 60 AD cases, a white matter disease (WMD) characterized by tissue rarefaction, mild gliosis and a non-amyloid small-vessel sclerosis occurred in the central, preferentially frontal deep white matter. The mean vessel density was significantly lower than in normal control case frontal white matter. The presence of WMD did not parallel the severity of grey matter Alzheimer encephalopathy. In 25 of 60 AD cases, white matter degeneration with signs of both condensation and rarefaction of tissue elements was seen subjacent to advanced cortical degeneration in the temporal lobes. It concurred with WMD in only 13 cases and was judged to be of anterograde, Wallerian type and not related to angiopathy. In VaD, similar changes occurred, accompanied by several types of focal and topographically related lesions. For diffuse white matter pathology of similar appearance in vascular and neurodegenerative disease with dementia, there may be various at least partly contrasting aetiologies, which can be differentiated by the presence of even minor focal lesions in some cases. For the recognition of such subtle variations in the spectrum of WMD, modern imaging techniques are crucial for detailed clinical diagnosis and attempts at therapeutic intervention.