Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients

Background: Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. Methods: Prospective study of healthy controls ( n = 19), CI ( n = 20), and NI ( n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. Results: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment ( p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF ( p = 0.06), while WM and cortical CBF accounted for 8.2% of variance ( p = 0.04). Conclusion: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

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Clinical and Radiological Correlates of Reduced CBF Measured Using MRI

Stroke ◽

10.1161/str.32.suppl_1.317-a ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 317-318

Author(s):

Vincent N Thijs ◽

Tobias Neumann-Haefelin ◽

Michael E Moseley ◽

Michael P Marks ◽

Gregory W Albers

Keyword(s):

Symptom Onset ◽

Cerebral Blood Volume ◽

Arterial Input Function ◽

Mean Transit Time ◽

Input Function ◽

Lesion Volume ◽

Time Curve ◽

Measured Concentration ◽

Ischemic Lesion ◽

Adc Values

11 Background and purpose Methods for determining CBF using IV bolus tracking MRI have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional cerebral blood flow (rCBF). We studied the clinical and radiological features of patients with severe reductions of rCBF on MRI and analysed the relationship between reduced rCBF and ADC. Methods We studied patients with non-lacunar acute ischemic stroke in whom PWI and DWI MRI were performed within 7 hours after symptom onset. A PWI>DWI mismatch of >20% was required. Maps of rCBF, cerebral blood volume (rCBV) and mean transit time (rMTT) were generated after deconvoluting the measured concentration-time curve with the arterial input function using singular value decomposition. The ischemic lesion was outlined on the MTT map and the region of interest (ROI) transferred to the rCBF and rCBV map. ADC-maps were calculated. ADC lesions were defined as regions with ADC values ≤ 550 μm m2/sec. We compared the characteristics of patients with ischemic lesions that had a relative CBF of <50% to the contralateral hemisphere to patients with lesions that had relative CBF of >50%. Characteristics analysed included age, time to MRI, baseline NIHSS, mean ADC, DWI lesion volume, PWI lesion volume and absolute mismatch volume. Results Fifteen patients with an initial PWI>DWI mismatch of >20% were included. Ten had lesions with rCBF of >50% (median 60%) and five patients had rCBF of <50% (median 27.7%). Patients with rCBF <50% had lower ADC values (median 431 μmm2/sec versus 506 μ mm2/sec, p=0.028), larger DWI volumes (median 75.6 cm 3 versus 8.6 cm 3 , p=0.001) and larger PWI lesions as defined by the MTT volume (median 193 cm 3 versus 69 cm 3 , p=0.028) and more severe baseline NIHSS scores (median 18 versus 9, p=0.019). The rMTT and rCBV of the lesions were similar in both groups, as were the age, the absolute mismatch volume and the time from symptom onset to MRI. Conclusion These data indicate that ischemic lesions with severe CBF reductions, measured with new MRI techniques, are associated with a lower mean ADC, larger DWI and PWI lesion volumes and a higher NIHSS score.

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Correlation between cognitive impairment and cerebral hemodynamic disturbances on perfusion magnetic resonance imaging in European adults with moyamoya disease

Journal of Neurosurgery ◽

10.3171/2010.4.jns091808 ◽

2010 ◽

Vol 113 (4) ◽

pp. 753-759 ◽

Cited By ~ 37

Author(s):

Lionel Calviere ◽

Isabelle Catalaa ◽

Fabienne Marlats ◽

Alain Viguier ◽

Fabrice Bonneville ◽

...

Keyword(s):

Cognitive Impairment ◽

Moyamoya Disease ◽

Cerebral Blood Volume ◽

Mean Transit Time ◽

Perfusion Magnetic Resonance Imaging ◽

Cerebrovascular Reserve ◽

Cerebral Hemodynamic ◽

Perfusion Mr ◽

Perfusion Mr Imaging ◽

Relationship Of

Object Although cognitive impairment has been reported in adults with moyamoya disease (MMD), its relationship with cerebral hemodynamic disturbances has not been investigated. The aims of the present study were to confirm the presence of dysexecutive cognitive syndrome (DCS) in adults with MMD and to explore the relationship of DCS with frontal lobe perfusion as measured by perfusion MR imaging. Methods Cerebral blood volume (CBV) ratio and mean transit time delay were measured in frontal and temporoparietal regions using the cerebellum as a reference region in 10 European adults with MMD. In addition, the authors calculated the cerebrovascular reserve (CVR) using the CBV ratio and the acetazolamide challenge. All patients underwent a standardized neuropsychological assessment test battery. The authors defined DCS as an impairment shown on 3 tests or more of executive function. Results The authors found DCS in 6 patients. The frontal CVR was lower in patients with DCS than in patients without DCS (mean ± SD: −13.5 ± 13.2% and 20.3 ± 21.3%; p = 0.019, Mann-Whitney U-test). Other parameters of frontal perfusion and temporoparietal CVR were not correlated with DCS. Conclusions The authors' findings suggest that DCS is common in European adults with MMD and may be related to frontal perfusion impairment.

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Relevance of hypointense brain MRI lesions for long-term worsening of clinical disability in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513494490 ◽

2013 ◽

Vol 20 (2) ◽

pp. 214-219 ◽

Cited By ~ 25

Author(s):

Antonio Giorgio ◽

Maria Laura Stromillo ◽

Maria Letizia Bartolozzi ◽

Francesca Rossi ◽

Marco Battaglini ◽

...

Keyword(s):

Multiple Sclerosis ◽

Brain Mri ◽

Univariate Analysis ◽

Brain Lesion ◽

Brain Magnetic Resonance Imaging ◽

Stepwise Multiple Regression ◽

Lesion Volume ◽

Magnetic Resonance Imaging Mri ◽

Relapsing Remitting Multiple Sclerosis

Background: The accrual of brain focal pathology is considered a good substrate of disability in relapsing–remitting multiple sclerosis (RRMS). However, knowledge on long-term lesion evolution and its relationship with disability progression is poor. Objective: The objective of this paper is to evaluate in RRMS the long-term clinical relevance of brain lesion evolution. Methods: In 58 RRMS patients we acquired, using the same scanner and protocol, brain magnetic resonance imaging (MRI) at baseline and 10±0.5 years later. MRI data were correlated with disability changes as measured by the Expanded Disability Status Scale (EDSS). Results: The annualized 10-year lesion volume (LV) growth was +0.25±0.5 cm3 (+6.7±8.7%) for T2-weighted (T2-W) lesions and +0.20±0.31 cm3 (+11.5±12.3%) for T1-weighted (T1-W) lesions. The univariate analysis showed moderate correlations between baseline MRI measures and EDSS at 10 years ( p < 0.001). Also, 10-year EDSS worsening correlated with LV growth and the number of new/enlarging lesions measured over the same period ( p < 0.005). In the stepwise multiple regression analysis, EDSS worsening over 10 years was best correlated with the combination of baseline T1-W lesion count and increasing T1-W LV ( R = 0.61, p < 0.001). Conclusion: In RRMS patients, long-term brain lesion accrual is associated with worsening in clinical disability. This is particularly true for hypointense, destructive lesions.

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Severity of Post-Stroke Cognitive Impairment Moderates the Relationship Between Cognitive Change and Emotional Distress in the Months Following Stroke

10.31234/osf.io/sxv52 ◽

2021 ◽

Author(s):

Miranda Wheeler ◽

Owen Williams ◽

Louise Johns ◽

Grace Chiu ◽

Elitsa D. Slavkova ◽

...

Keyword(s):

Cognitive Impairment ◽

Cognitive Rehabilitation ◽

Process Model ◽

Emotional Adjustment ◽

Depression Scale ◽

Cognitive Change ◽

Cognitively Impaired ◽

Psychological Consequences ◽

Post Stroke ◽

Cognitive Improvement

Depression and anxiety are common psychological consequences of stroke. Here, we investigated the relationships between cognitive change following stroke, awareness of cognitive impairments, and mood to further understanding of change processes influencing psychological outcomes post-stroke in line with the “Y-shaped” process model. Stroke patients (n = 143) were assessed at 3-weeks (T1) and 6-months (T2) post stroke and had completed the Oxford Cognitive Screen (T1 and T2), the Cognitive Failures Questionnaire (CFQ; T2), and the Hospital Anxiety and Depression Scale (HADS; T2). An ANCOVA controlling for disability relating to activities of daily living (ADL) revealed that awareness of cognitive impairment was significantly lower in participants with moderate-severe cognitive impairment. Regression analysis indicated that greater awareness of cognitive impairment and greater independence in ADL were associated with lower HADS scores at T2. Finally, cognitive improvement over time was associated with lower HADS scores at T2. This was moderated by acute cognitive impairment, suggesting that this effect was largest for those most cognitively impaired at T1. Together, predictors explained 36.9% variance in the model, whereby the interaction variable explained 2.2% variance. Targeting those most cognitively impaired post-stroke with cognitive rehabilitation may positively impact their long-term emotional adjustment.

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Abstract T P37: Cerebral Blood Volume Does Not Differentiate Regions With Persistent Cerebral Hypoperfusion That Infarct From Those That Survive: A DEFUSE 2 Substudy

Stroke ◽

10.1161/str.45.suppl_1.tp37 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Sharan K Mann ◽

Soren Christensen ◽

Michael Mlynash ◽

Stephanie Kemp ◽

Maarten G Lansberg ◽

...

Keyword(s):

Blood Flow ◽

Blood Volume ◽

Cerebral Blood Volume ◽

Mean Transit Time ◽

T Test ◽

Cerebral Hypoperfusion ◽

Lesion Volume ◽

Mri Scan ◽

Paired T Test

Background: The optimal Tmax threshold for predicting critically hypoperfused tissue is a delay of >6 seconds. However, persistent Tmax >6s lesions do not invariably progress to infarction. Differences in cerebral blood volume (CBV) may explain why some regions of persistent cerebral hypoperfusion (PCHP) infarct whereas others survive. We hypothesized that CBV is higher in areas of PCHP that survive versus those that infarct. Methods: We included patients that had: 1) a Tmax >6s lesion on baseline and early follow-up MRI perfusion scans, and 2) a FLAIR lesion on the day 5 MRI scan. Regions of PCHP had to meet two criteria: 1) Tmax >6s positive on both baseline and co-registered early follow-up MRI perfusion scans, and 2) DWI negative on the baseline MRI scan. PCHP regions were classified as PCHP-infarct if there was a corresponding lesion on the co-registered 5 day FLAIR and as PCHP-survival if there was no corresponding lesion. Patients with no region of either PCHP-infarct or PCHP-survival were excluded. The study had two parts. In part 1, the paired t-test was used to compare lesion volume, CBV, cerebral blood flow (CBF), mean transit time (MTT), and Tmax between PCHP-infarct and PCHP-survival regions within each patient. In part 2, the 2-sample t-test was used to compare mean volume, CBV, CBF, MTT, and Tmax in PCHP-infarct and PCHP-survival regions for all patients together as a group. Results: 61 patients were included in the analysis. Mean total PCHP volume was 26cc (16cc infarct, 10cc survival) and median total PCHP volume was 15cc (9cc infarct, 6cc survival). For part 1, CBV was not different in PCHP-infarct versus PCHP-survival (P=0.16). CBF was higher (P=0.05) in regions of PCHP-survival, and MTT and Tmax were less prolonged (P=0.03 and P < 0.01). For part 2, mean CBV and MTT did not differ between PCHP-infarct and PCHP-survival (P=0.23 and P=0.40). Mean CBF trended higher (P=0.07) and mean Tmax delays were milder (P= 0.04) in PCHP-survival. Conclusion: CBV does not differ between regions of PCHP-infarct versus PCHP-survival and does not explain why some areas of persistent, severe hypoperfusion survive. Tmax was less severely delayed and CBF values were higher in regions of PCHP-survival, which warrant further study.

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Predictive Value of the Velocity of Collateral Filling in Patients with Acute Ischemic Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.182 ◽

2014 ◽

Vol 35 (2) ◽

pp. 206-212 ◽

Cited By ~ 21

Author(s):

Sebastian E Beyer ◽

Louisa von Baumgarten ◽

Kolja M Thierfelder ◽

Marietta Rottenkolber ◽

Hendrik Janssen ◽

...

Keyword(s):

Cerebral Blood Volume ◽

Ct Perfusion ◽

Mean Transit Time ◽

Intravenous Thrombolysis ◽

Lesion Size ◽

Small Lesion ◽

Time Resolved ◽

Time To Peak ◽

Magnetic Resonance Imaging Mri

The velocity of collateral filling can be assessed in dynamic time-resolved computed tomography (CT) angiographies and may predict initial CT perfusion (CTP) and follow-up lesion size. We included all patients with an M1± internal carotid artery (ICA) occlusion and follow-up imaging from an existing cohort of 1791 consecutive patients who underwent multimodal CT for suspected stroke. The velocity of collateral filling was quantified using the delay of time-to-peak (TTP) enhancement of the M2 segment distal to the occlusion. Cerebral blood volume (CBV) and mean transit time (MTT)-CBV mismatch were assessed in initial CTP. Follow-up lesion size was assessed by magnetic resonance imaging (MRI) or non-enhanced CT (NECT). Multivariate analyses were performed to adjust for extent of collateralization and type of treatment. Our study comprised 116 patients. Multivariate analysis showed a short collateral blood flow delay to be an independent predictor of a small CBV lesion ( P<0.001) and a large relative mismatch ( P<0.001) on initial CTP, of a small follow-up lesion ( P<0.001), and of a small difference between initial CBV and follow-up lesion size ( P=0.024). Other independent predictors of a small lesion on follow-up were a high morphologic collateral grade ( P=0.001), lack of an additional ICA occlusion ( P=0.009), and intravenous thrombolysis ( P=0.022). Fast filling of collaterals predicts initial CTP and follow-up lesion size and is independent of extent of collateralization.

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Perfusion Changes in Acute Stroke Treated with Theophylline as an Add-on to Thrombolysis

Clinical Neuroradiology ◽

10.1007/s00062-021-01029-x ◽

2021 ◽

Author(s):

Boris Modrau ◽

Anthony Winder ◽

Niels Hjort ◽

Martin Nygård Johansen ◽

Grethe Andersen ◽

...

Keyword(s):

Clinical Trials ◽

Cerebral Blood Volume ◽

Neuroprotective Effect ◽

Mean Transit Time ◽

Control Group ◽

Infarct Core ◽

Treatment Groups ◽

Stroke Models ◽

Magnetic Resonance Imaging Mri

Abstract Purpose Theophylline has been suggested to have a neuroprotective effect in ischemic stroke; however, results from animal stroke models and clinical trials in humans are controversial. The aim of this study was to assess the effect of theophylline on the cerebral perfusion with multiparametric magnetic resonance imaging (MRI). Methods The relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) in the infarct core, penumbra, and unaffected tissue were measured using multi-parametric MRI at baseline and 3‑h follow-up in patients treated with theophylline or placebo as an add-on to thrombolytic therapy. Results No significant differences in mean rCBF, rCBV, and rMTT was found in the penumbra and unaffected tissue between the theophylline group and the control group between baseline and 3‑h follow-up. In the infarct core, mean rCBV increased on average by 0.05 in the theophylline group and decreased by 0.14 in the control group (p < 0.04). Mean rCBF and mean rMTT in the infarct core were similar between the two treatment groups. Conclusion The results indicate that theophylline does not change the perfusion in potentially salvageable penumbral tissue but only affects the rCBV in the infarct core. In contrast to the penumbra, the infarct core is unlikely to be salvageable, which might explain why theophylline failed in clinical trials.

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Are depressive symptoms in mild cognitive impairment predictive of conversion to dementia?

International Psychogeriatrics ◽

10.1017/s1041610215002409 ◽

2016 ◽

Vol 28 (6) ◽

pp. 921-928 ◽

Cited By ~ 3

Author(s):

Ellen De Roeck ◽

Ingrid Ponjaert-Kristoffersen ◽

Marc Bosmans ◽

Peter Paul De Deyn ◽

Sebastiaan Engelborghs ◽

...

Keyword(s):

Cognitive Impairment ◽

Depressive Symptoms ◽

Mild Cognitive Impairment ◽

Geriatric Depression Scale ◽

Depression Scale ◽

Cued Recall ◽

Cognitive Testing ◽

Cognitive Measures ◽

Significant Difference

ABSTRACTBackground:Depressive symptoms are common in amnestic mild cognitive impairment (aMCI). The association between depressive symptoms and conversion to dementia is not yet clear. This longitudinal study was conducted to ascertain whether depressive symptoms in aMCI patients are predictive of conversion to dementia.Methods:35 aMCI patients participated in this study. All participants underwent cognitive testing and were administered the geriatric depression scale (GDS) to determine the presence of depressive symptoms. A score equaling or higher than 11 on the GDS was taken as the cut-off point for presence of significant depressive symptoms. Conversion to dementia was assessed at follow-up visits after 1.5, 4, and 10 years.Results:31.4% of the patients reported depressive symptoms at baseline. None of the cognitive measures revealed a significant difference at baseline between patients with and without depressive symptoms. After 1.5, 4, and 10 years respectively 6, 14, and 23 patients had converted to dementia. Although the GDS scores at baseline did not predict conversion to dementia, the cognitive measures and more specifically a verbal cued recall task (the memory impairment scale-plus) was a good predictor for conversion.Conclusions:Based on this dataset, the presence of depressive symptoms in aMCI patients is not predictive of conversion to dementia.

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Regional hippocampal involvement and cognitive impairment in pediatric multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515598569 ◽

2015 ◽

Vol 22 (5) ◽

pp. 628-640 ◽

Cited By ~ 13

Author(s):

Maria A Rocca ◽

Maria E Morelli ◽

Maria P Amato ◽

Lucia Moiola ◽

Angelo Ghezzi ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Multiple Sclerosis ◽

Cognitive Impairment ◽

Magnetic Resonance ◽

Dentate Gyrus ◽

Hippocampal Volume ◽

Cognitively Impaired ◽

Lesion Volume ◽

Resonance Imaging ◽

Pediatric Multiple Sclerosis

Objectives: We assessed global and regional hippocampal volume abnormalities in pediatric multiple sclerosis (MS) patients and their correlations with clinical, neuropsychological and magnetic resonance imaging metrics. Methods: From 53 pediatric MS patients and 18 healthy controls, global hippocampal volume was computed using a manual tracing procedure. Regional hippocampal volume modifications were assessed using a radial mapping analysis. MS patients with abnormal performance in three or more tests of a neuropsychological battery for children were classified as cognitively impaired. Results: Global hippocampal volume was reduced in MS patients compared with controls, but did not correlate with clinical, neuropsychological and magnetic resonance imaging measures. Compared to controls, MS patients experienced bilateral radial atrophy of the cornu ammonis, subiculum and dentate gyrus subfields as well as radial hypertrophy of the dentate gyrus subfield. Regional hippocampal volume modifications correlated with brain T2 lesion volume as well as attention and language abilities. Global hippocampal volume did not differ between cognitively impaired ( n=12) and cognitively preserved MS patients. Compared to cognitively preserved, cognitively impaired MS patients had atrophy of the subiculum and dentate gyrus subfields of the right hippocampus. Conclusions: Hippocampal subregions have different vulnerability to damage in pediatric MS. Regional rather than global hippocampal involvement contributes to global cognitive impairment as well as to deficits of selected cognitive tests.

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Families, Caregivers, and Assistance

Dementia with Lewy Body and Parkinson's Disease Patients ◽

10.1093/oso/9780199977567.003.0033 ◽

2013 ◽

Author(s):

J. Eric Ahlskog

Keyword(s):

Decision Making ◽

Cognitive Impairment ◽

Family Business ◽

Psychometric Testing ◽

Cognitive Testing ◽

Cognitively Impaired ◽

Leadership Positions ◽

Hand Dexterity ◽

The Family ◽

Cognitive Problems

By definition, those with DLB or PDD are cognitively impaired. The degree of cognitive impairment is highly variable; some people remain relatively compensated and stable for years. For others, confusion impairs even the simplest of activities. Unlike Alzheimer’s disease, in which dementia occurs in isolation, DLB and PDD are often associated with other problems: gait and balance dysfunction; impairment of hand dexterity; the bowel, bladder, and blood pressure problems of dysautonomia. The challenges to not only the affected person, but also the spouse or partner and family can be substantial. Caregivers may have many responsibilities, and restructured lives become the rule. These issues are so variable that a one-size-fits-all approach is not realistic. Once DLB or PDD has been diagnosed, it is wise for the spouse, partner, or family to discuss with the affected patient whether revisions in decision-making should be addressed. Occasional people with DLB or PDD have relatively limited cognitive problems, and for these individuals perhaps no major changes in the family business or finances are necessary. However, this issue should still be discussed. Investments, taxes, and bill-paying may need to be switched to another family member or spouse. A family business may need new leadership. In some cases, leadership positions may be retained, but with an advisor who reviews all important decisions. When there is uncertainty, formal cognitive testing may provide important insight. Psychologists typically offer psychometric testing, assessing various aspects of cognition. The interpretation of these findings can be translated into implications for decision-making. One of the most disabling restrictions placed on someone in our society is the removal of driving privileges. Communities are no longer structured where one can simply walk to the store, church, or synagogue. In the setting of DLB or PDD, however, driving restrictions or limitations may be appropriate. At least the possibility should be discussed. Driving may be compromised by both cognitive impairment and parkinsonism. Usually it is the cognitive problems that are the greater threat to the driver and public safety.

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