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To evaluate the frequency and spectrum of lesions of different pelvic floor muscles at endoanal MRI in women with severe faecal incontinence and to study their relation with incontinence severity and manometric findings. In 105 women MRI examinations were evaluated for internal anal sphincter (IAS), external anal sphincter (EAS), puborectal muscle (PM) and levator ani (LA) lesions. The relative contribution of lesions to differences in incontinence severity and manometric findings was studied. IAS (n = 59) and EAS (n = 61) defects were more common than PM (n = 23) and LA (n = 26) defects. PM and LA defects presented mainly with IAS and/or EAS defects (isolated n = 2 and n = 3). EAS atrophy (n = 73) was more common than IAS (n = 19), PM (n = 16) and LA (n = 9) atrophy and presented mainly isolated. PM and LA atrophy presented primarily with EAS atrophy (isolated n = 3 and n = 1). Patients with IAS and EAS lesions had a lower resting and squeeze pressure, respectively; no other associations were found. PM and LA lesions are relatively common in patients with severe faecal incontinence, but the majority of lesions are found in women who also have IAS and/or EAS lesions. Only an association between anal sphincter lesions and manometry was observed. [ABSTRACT FROM AUTHOR]

Delirium is associated with long-term cognitive dysfunction and with increased brain atrophy. However, it is unclear whether these problems result from or predisposes to delirium. We aimed to investigate preoperative to postoperative brain changes, as well as the role of delirium in these changes over time. We investigated the effects of surgery and postoperative delirium with brain MRIs made before and 3 months after major elective surgery in 299 elderly patients, and an MRI with a 3 months follow-up MRI in 48 non-surgical control participants. To study the effects of surgery and delirium, we compared brain volumes, white matter hyperintensities and brain infarcts between baseline and follow-up MRIs, using multiple regression analyses adjusting for possible confounders. Within the patients group, 37 persons (12%) developed postoperative delirium. Surgical patients showed a greater decrease in grey matter volume than non-surgical control participants [linear regression: B (95% confidence interval) = -0.65% of intracranial volume (-1.01 to -0.29, P < 0.005)]. Within the surgery group, delirium was associated with a greater decrease in grey matter volume [B (95% confidence interval): -0.44% of intracranial volume (-0.82 to -0.06, P = 0.02)]. Furthermore, within the patients, delirium was associated with a non-significantly increased risk of a new postoperative brain infarct [logistic regression: odds ratio (95% confidence interval): 2.8 (0.7-11.1), P = 0.14]. Our study was the first to investigate the association between delirium and preoperative to postoperative brain volume changes, suggesting that delirium is associated with increased progression of grey matter volume loss., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Objectives: Posttreatment radiologic deterioration of an irradiated high-grade (WHO grade 3-4) glioma (HGG) may be the result of true progressive disease or treatment-induced effects (TIE). Differentiation between these entities is of great importance but remains a diagnostic challenge. This study assesses the diagnostic value of conventional MRI characteristics to differentiate progressive disease from TIE in HGGs., Methods: In this single-center, retrospective, consecutive cohort study, we included adults with a HGG who were treated with (chemo-)radiotherapy and subsequently developed a new or increasing contrast-enhancing lesion on conventional follow-up MRI. TIE and progressive disease were defined radiologically as stable/decreased for ≥6 weeks or Response Assessment in Neuro-Oncology progression and histologically as TIE without viable tumor or progressive disease. Two neuroradiologists assessed 21 preselected MRI characteristics of the progressive lesions. The statistical analysis included logistic regression to develop a full multivariable model, a diagnostic model with model reduction, and a Cohen kappa interrater reliability (IRR) coefficient., Results: A total of 210 patients (median age 61 years, interquartile range 54-68, 189 male) with 284 lesions were included, of whom 141 (50%) had progressive disease. Median time to progressive disease was 2 (0.7-6.1) and to TIE 0.9 (0.7-3.5) months after radiotherapy. After multivariable modeling and model reduction, the following determinants prevailed: radiation dose (odds ratio [OR] 0.68, 95% CI 0.49-0.93), longer time to progression (TTP; OR 3.56, 95% CI 1.84-6.88), marginal enhancement (OR 2.04, 95% CI 1.09-3.83), soap bubble enhancement (OR 2.63, 95% CI 1.39-4.98), and isointense apparent diffusion coefficient (ADC) signal (OR 2.11, 95% CI 1.05-4.24). ORs >1 indicate higher odds of progressive disease. The Hosmer & Lemeshow test showed good calibration ( p = 0.947) and the area under the receiver operating characteristic curve was 0.722 (95% CI 0.66-0.78). In the glioblastoma subgroup, TTP, marginal enhancement, and ADC signal were significant. IRR analysis between neuroradiologists revealed moderate to near perfect agreement for the predictive items but poor agreement for others., Discussion: Several characteristics from conventional MRI are significant predictors for the discrimination between progressive disease and TIE. However, IRR was variable. Conventional MRI characteristics from this study should be incorporated into a multimodal diagnostic model with advanced imaging techniques., Classification of Evidence: This study provides Class II evidence that in patients with irradiated HGGs, radiation dose, longer TTP, marginal enhancement, soap bubble enhancement, and isointense ADC signal distinguish progressive disease from TIE., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28-2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18-7.43), cortical infarcts (RR = 5.28, 95%CI 2.91-9.55), lacunes (RR = 5.66, 95%CI 2.85-11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27-5.84) and decreased cerebral blood flow (RR = 1.35 per -100 ml/min, 95%CI 1.00-1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05-0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.

The etiology of cerebral small vessel disease (CSVD) is the subject of ongoing research. Although intracranial atherosclerosis (ICAS) has been proposed as a possible cause, studies on their relationship remain sparse. We used 7 T vessel wall magnetic resonance imaging (MRI) to study the association between intracranial vessel wall lesions-a neuroimaging marker of ICAS-and MRI features of CSVD. Within the SMART-MR study, cross-sectional analyses were performed in 130 patients (68 ± 9 years; 88% male). ICAS burden-defined as the number of vessel wall lesions-was determined on 7 T vessel wall MRI. CSVD features were determined on 1.5 T and 7 T MRI. Associations between ICAS burden and CSVD features were estimated with linear or modified Poisson regression, adjusted for age, sex, vascular risk factors, and medication use. In 125 patients, ≥1 vessel wall lesions were found (mean 8.5 ± 5.7 lesions). ICAS burden (per + 1 SD) was associated with presence of large subcortical and/or cortical infarcts (RR = 1.65; 95%CI: 1.12-2.43), lacunes (RR = 1.45; 95% CI: 1.14-1.86), cortical microinfarcts (RR = 1.48; 95%CI: 1.13-1.94), and total white matter hyperintensity volume ( b  = 0.24; 95%CI: 0.02-0.46). Concluding, patients with a higher ICAS burden had more CSVD features, although no evidence of co-location was observed. Further longitudinal studies are required to determine if ICAS precedes development of CSVD.

The relevance of intracranial vessel wall lesions detected with MRI is not fully established. In this study (trial identification number: NTR2119; www.trialregister.nl), 7T MRI was used to investigate if a higher vessel wall lesion burden is associated with more cerebral parenchymal changes in patients with ischemic stroke or transient ischemic attack (TIA). MR images of 82 patients were assessed for the number of vessel wall lesions of the large intracranial arteries and for cerebral parenchymal changes, including the presence and number of cortical, small subcortical, and deep gray matter infarcts; lacunes of presumed vascular origin; cortical microinfarcts; and periventricular and deep white matter hyperintensities (WMHs). Regression analyses showed that a higher vessel wall lesion burden was associated with the presence of small subcortical infarcts, lacunes of presumed vascular origin, and deep gray matter infarcts (relative risk 1.18; 95% CI, 1.03-1.35) and presence of moderate-to-severe periventricular WMHs (1.21; 95% CI, 1.03-1.42), which are all manifestations of small vessel disease (SVD). The burden of enhancing vessel wall lesions was associated with the number of cortical microinfarcts only (1.48; 95% CI, 1.04-2.11). These results suggest an interrelationship between large vessel wall lesion burden and cerebral parenchymal manifestations often linked to SVD or, alternatively, that vascular changes occur in both large and small intracranial arteries simultaneously., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lindenholz, de Bresser, van der Kolk, van der Worp, Witkamp, Hendrikse and van der Schaaf.)

The underlying structural correlates of predisposition to postoperative delirium remain largely unknown. A combined analysis of preoperative brain magnetic resonance imaging (MRI) markers could improve our understanding of the pathophysiology of delirium. Therefore, we aimed to identify different MRI brain phenotypes in older patients scheduled for major elective surgery, and to assess the relation between these phenotypes and postoperative delirium. Markers of neurodegenerative and neurovascular brain changes were determined from MRI brain scans in older patients (n = 161, mean age 71, standard deviation 5 years), of whom 24 (15%) developed delirium. A hierarchical cluster analysis was performed. We found six distinct groups of patients with different MRI brain phenotypes. Logistic regression analysis showed a higher odds of developing postoperative delirium in individuals with multi-burden pathology (n = 15 (9%), odds ratio (95% confidence interval): 3.8 (1.1-13.0)). In conclusion, these results indicate that different MRI brain phenotypes are related to a different risk of developing delirium after major elective surgery. MRI brain phenotypes could assist in an improved understanding of the structural correlates of predisposition to postoperative delirium., (Copyright © 2021. Published by Elsevier Inc.)

Objective: This study aimed at developing a quantitative approach to assess abnormalities on MRI of the brachial plexus and the cervical roots in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) and to evaluate interrater reliability and its diagnostic value., Methods: We performed a cross-sectional study in 50 patients with CIDP, 31 with MMN and 42 disease controls. We systematically measured cervical nerve root sizes on MRI bilaterally (C5, C6, C7) in the coronal [diameter (mm)] and sagittal planes [area (mm 2 )], next to the ganglion (G 0 ) and 1 cm distal from the ganglion (G 1 ). We determined their diagnostic value using a multivariate binary logistic model and ROC analysis. In addition, we evaluated intra- and interrater reliability., Results: Nerve root size was larger in patients with CIDP and MMN compared to controls at all predetermined anatomical sites. We found that nerve root diameters in the coronal plane had optimal reliability (intrarater ICC 0.55-0.87; interrater ICC 0.65-0.90). AUC was 0.78 (95% CI 0.69-0.87) for measurements at G 0 and 0.81 (95% CI 0.72-0.91) for measurements at G 1 . Importantly, our quantitative assessment of brachial plexus MRI identified an additional 10% of patients that showed response to treatment, but were missed by nerve conduction (NCS) and nerve ultrasound studies., Conclusion: Our study showed that a quantitative assessment of brachial plexus MRI is reliable. MRI can serve as an important additional diagnostic tool to identify treatment-responsive patients, complementary to NCS and nerve ultrasound.

BACKGROUND AND PURPOSE: Hyperglycemia can lead to an increased rate of apoptosis of microglial cells and to damaged neurons. The relation between hyperglycemia and cerebrovascular markers on MRI is unknown. Our aim was to study the association between intraoperative hyperglycemia and cerebrovascular markers. METHODS: In this further analysis of a subgroup investigation of the BIOCOG study, 65 older non-demented patients (median 72 years) were studied who underwent elective surgery of ≥ 60 minutes. Intraoperative blood glucose maximum was determined retrospectively in each patient. In these patients, preoperatively and at 3 months follow-up a MRI scan was performed and white matter hyperintensity (WMH) volume and shape, infarcts, and perfusion parameters were determined. Multivariable logistic regression analyses were performed to determine associations between preoperative cerebrovascular markers and occurrence of intraoperative hyperglycemia. Linear regression analyses were performed to assess the relation between intraoperative hyperglycemia and pre- to postoperative changes in WMH volume. Associations between intraoperative hyperglycemia and postoperative WMH volume at 3 months follow-up were also assessed by linear regression analyses. RESULTS: Eighteen patients showed intraoperative hyperglycemia (glucose maximum ≥ 150 mg/dL). A preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia [convexity: OR 33.318 (95 % CI (1.002 - 1107.950); p = 0.050]. Other preoperative cerebrovascular markers were not related to the occurrence of intraoperative hyperglycemia. Intraoperative hyperglycemia showed no relation with pre- to postoperative changes in WMH volume nor with postoperative WMH volume at 3 months follow-up. CONCLUSIONS: We found that a preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia. These findings may suggest that a similar underlying mechanism leads to a certain pattern of vascular brain abnormalities and an increased risk of hyperglycemia., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Delirium is a frequent complication after surgery with important negative outcomes for affected patients and society. However, it is still largely unknown why some patients have a predisposition for delirium and others not. To increase our understanding of the neural substrate of postoperative delirium, we studied the association between preoperative brain MRI features and the occurrence of delirium after major surgery., Methods: A group of 413 patients without dementia (Mean 72 years, SD: 5) was included in a prospective observational two-center study design. The study was conducted at Charité Universitätsmedizin (Berlin, Germany) and the University Medical Center Utrecht (Utrecht, The Netherlands). We measured preoperative brain volumes (total brain, gray matter, white matter), white matter hyperintensity volume and shape, brain infarcts and cerebral perfusion, and used logistic regression analysis adjusted for age, sex, intracranial volume, study center and type of surgery., Results: Postoperative delirium was present in a total of 70 patients (17%). Preoperative cortical brain infarcts increased the risk of postoperative delirium, although this did not reach statistical significance (OR (95%CI): 1.63 (0.84-3.18). Furthermore, we found a trend for an association of a more complex shape of white matter hyperintensities with occurrence of postoperative delirium (OR (95%CI): 0.97 (0.95-1.00)). Preoperative brain volumes, white matter hyperintensity volume, and cerebral perfusion were not associated with occurrence of postoperative delirium., Conclusion: Our study suggests that patients with preoperative cortical brain infarcts and those with a more complex white matter hyperintensity shape may have a predisposition for developing delirium after major surgery., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Magnetic resonance imaging of the brachial plexus shows nerve thickening in approximately half of the patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The reliability of qualitative evaluation of brachial plexus MRI has not been studied previously., Methods: We performed an interrater study in a retrospective cohort of 19 patients with CIDP, 17 patients with MMN, and 14 controls. The objective was to assess interrater variability between radiologists by using a predefined scoring system that allowed the distinction of no, possible, or definite nerve thickening., Results: Raters agreed in 26 of 50 (52%) brachial plexus images; κ-coefficient was 0.30 (SE 0.08, 95% confidence interval 0.14-0.46, P < .0005)., Discussion: Our results provide evidence that interrater reliability of qualitative evaluation of brachial plexus MRI is low. Objective criteria for abnormality are required to optimize the diagnostic value of MRI for inflammatory neuropathies., (© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.)

Neurodegenerative and neurovascular diseases lead to heterogeneous brain abnormalities. A combined analysis of these abnormalities by phenotypes of the brain might give a more accurate representation of the underlying aetiology. We aimed to identify different MRI phenotypes of the brain and assessed the risk of future stroke and mortality within these subgroups. In 1003 patients (59 ± 10 years) from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, different quantitative 1.5T brain MRI markers were used in a hierarchical clustering analysis to identify 11 distinct subgroups with a different distribution in brain MRI markers and cardiovascular risk factors, and a different risk of stroke (Cox regression: from no increased risk compared to the reference group with relatively few brain abnormalities to HR = 10.34; 95% CI 3.80↔28.12 for the multi-burden subgroup) and mortality (from no increased risk compared to the reference group to HR = 4.00; 95% CI 2.50↔6.40 for the multi-burden subgroup). In conclusion, within a group of patients with manifest arterial disease, we showed that different MRI phenotypes of the brain can be identified and that these were associated with different risks of future stroke and mortality. These MRI phenotypes can possibly classify individual patients and assess their risk of future stroke and mortality.

Delirium, the clinical expression of acute encephalopathy, is a common neuropsychiatric syndrome that is related to poor outcomes, such as long-term cognitive impairment. Disturbances of functional brain networks are hypothesized to predispose for delirium. The aim of this study in non-delirious elderly individuals was to investigate whether predisposing risk factors for delirium are associated with fMRI network characteristics that have been observed during delirium. As predisposing risk factors, we studied age, alcohol misuse, cognitive impairment, depression, functional impairment, history of transient ischemic attack or stroke, and physical status. In this multicenter study, we included 554 subjects and analyzed resting-state fMRI data from 222 elderly subjects (63% male, age range: 65-85 year) after rigorous motion correction. Functional network characteristics were analyzed and based on the minimum spanning tree (MST). Global functional connectivity strength, network efficiency (MST diameter) and network integration (MST leaf fraction) were analyzed, as these measures were altered during delirium in previous studies. Linear regression analyses were used to investigate the relation between predisposing delirium risk factors and delirium-related fMRI characteristics, adjusted for confounding and multiple testing. Predisposing risk factors for delirium were not associated with delirium-related fMRI network characteristics. Older age within our elderly cohort was related to global functional connectivity strength (β = 0.182, p < 0.05), but in the opposite direction than hypothesized. Delirium-related functional network impairments can therefore not be considered as the common mechanism for predisposition for delirium., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Vascular risk factors have been associated with risk of Alzheimer's disease (AD) and volume loss of the hippocampus, but the associations with subfields of the hippocampus are understudied. Knowing if vascular risk factors contribute to hippocampal subfield atrophy may improve our understanding of vascular contributions to neurodegenerative diseases., Objective: To investigate the associations between age, sex, and vascular risk factors with hippocampal subfields volumes on 7T MRI in older persons without dementia., Methods: From the Medea 7T study, 283 participants (67±9 years, 68% men) without dementia had 7T brain MRI and hippocampal subfield segmentation. Subfields were automatically segmented on the 3D T2-weighted 7T images with ASHS software. Using linear mixed models, we estimated adjusted associations of age, sex, and vascular risk factors with z-scores of volumes of the entorhinal cortex (ERC), subiculum (SUB), Cornu Ammonis (CA)1, CA2, CA3, CA4, and dentate gyrus (DG), and tail as multivariate correlated outcomes., Results: Increasing age was associated with smaller volumes in all subfields, except CA4/DG. Current smoking was associated with smaller ERC and SUB volumes; moderate alcohol use with smaller CA1 and CA4/DG, obesity with smaller volumes of ERC, SUB, CA2, CA3, and tail; and diabetes mellitus with smaller SUB volume. Sex, former smoking, and hypertension were not associated with subfield volumes. When formally tested, no risk factor affected the subfield volumes differentially., Conclusion: Several vascular risk factors were associated with smaller volumes of specific hippocampal subfields. However, no statistical evidence was found that subfields were differentially affected by these risk factors.

Lacunes and white matter hyperintensities (WMHs) are features of cerebral small vessel disease (CSVD) that are associated with poor functional outcomes. However, how the two are related remains unclear. In this study, we examined the association between lacunes and several WMH features in patients with a history of vascular disease. A total of 999 patients (mean age 59 ± 10 years) with a 1.5 T brain magnetic resonance imaging (MRI) scan were included from the SMART-MR study. Lacunes were scored visually and WMH features (volume, subtype and shape) were automatically determined. Analyses consisted of linear and Poisson regression adjusted for age, sex, and total intracranial volume (ICV). Patients with lacunes (n = 188; 19%) had greater total (B = 1.03, 95% CI: 0.86 to 1.21), periventricular/confluent (B = 1.08, 95% CI: 0.89 to 1.27), and deep (B = 0.71, 95% CI: 0.44 to 0.97) natural log-transformed WMH volumes than patients without lacunes. Patients with lacunes had an increased risk of confluent type WMHs (RR = 2.41, 95% CI: 1.98 to 2.92) and deep WMHs (RR = 1.41, 95% CI: 1.22 to 1.62) and had a more irregular shape of confluent WMHs than patients without lacunes, independent of total WMH volume. In conclusion, we found that lacunes on MRI were associated with WMH features that correspond to more severe small vessel changes, mortality, and poor functional outcomes.

Background: Cerebral ischaemia is thought to be an important determinant of cognitive outcome after aneurysmal subarachnoid haemorrhage (aSAH), but the exact relationship is unclear. We studied the effect of ischaemic brain lesions during clinical course on cognitive outcome 2 months after aSAH., Methods: We studied 74 consecutive patients admitted to the University Medical Center Utrecht who had MRI post-coiling (3-21 days post-aSAH) and neuropsychological examination at 2 months. An ischaemic lesion was defined as hyperintensity on T2-FLAIR and DWI images. We measured both cognitive complaints (subjective) and cognitive functioning (objective). The relationship between ischaemic brain lesions and cognitive outcome was analysed by logistic regression analyses., Results: In 40 of 74 patients (54%), 152 ischaemic lesions were found. The median number of lesions per patient was 2 (1-37) and the median total lesion volume was 0.2 (0-17.4) mL. No difference was found between the group with and the group without ischaemic lesions with respect to the frequency of cognitive complaints. In the group with ischaemic lesions, significantly more patients (55%) showed poor cognitive functioning compared to the group without ischaemic lesions (26%) (OR 3.4, 95% CI 1.3-9.1). We found no relationship between the number and volume of the ischaemic lesions and cognitive functioning., Conclusions: Ischaemic brain lesions detected on MRI during clinical course after aSAH is a marker for poor cognitive functioning 2 months after aSAH, irrespective of the number or volume of the ischaemic lesions. Network or connectivity studies are needed to better understand the relationship between location of the ischaemic brain lesions and cognitive functioning.

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.

Small infarcts are among the key imaging features of cerebral small vessel disease (CSVD), but remain largely undetected on conventional MRI. We aimed to evaluate (1) imaging criteria for the detection of small infarcts in the caudate nucleus on 7T MRI, (2) intra- and inter-rater agreement, (3) frequency and (4) detection rate on 7T versus 1.5T MRI. In 90 patients (68 ± 8 years) with a history of vascular disease from the SMART-MR study, we defined 7T imaging criteria for cavitated and non-cavitated small infarcts in the caudate nucleus. In a separate set of 23 patients from the SMART study, intra-rater and inter-rater agreement was excellent for presence, number, and individual locations (Kappa's, ICCs, and Dice similarity coefficients ranged from 0.85 to 1.00). In the 90 patients, 21 infarcts (20 cavitated) in 12 patients were detected on 7T (13%) compared to 7 infarcts in 6 patients on 1.5T (7%). In conclusion, we established reproducible imaging criteria for the detection of small infarcts in the caudate nucleus on 7T MRI and showed that 7T MRI allows for a higher detection rate than conventional 1.5T MRI. These imaging criteria can be used in future studies to provide new insights into the pathophysiology of CSVD.

Objective: A substantial part of non-traumatic intracerebral haemorrhages (ICH) arises from a macrovascular cause, but there is little guidance on selection of patients for additional diagnostic work-up. We aimed to develop and externally validate a model for predicting the probability of a macrovascular cause in patients with non-traumatic ICH., Methods: The DIagnostic AngioGRAphy to find vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a prospective, multicentre study assessing yield and accuracy of CT angiography (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter angiography in diagnosing macrovascular causes in patients with non-traumatic ICH. We considered prespecified patient and ICH characteristics in multivariable logistic regression analyses as predictors for a macrovascular cause. We combined independent predictors in a model, which we validated in an external cohort of 173 patients with ICH (78 macrovascular cause, 45%)., Results: Independent predictors were younger age, lobar or posterior fossa (vs deep) location of ICH, and absence of small vessel disease (SVD). A model that combined these predictors showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to 0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI 0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91; 95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to 0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or posterior fossa ICH without SVD., Conclusion: The DIAGRAM scores help to predict the probability of a macrovascular cause in patients with non-traumatic ICH based on age, ICH location, SVD and CTA., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

Study Question: What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage?, Methods: This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up., Study Answer and Limitations: A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced permanent sequelae. Not all patients with negative CT angiography and MRI/MRA results underwent DSA. Although the previous probability of finding a macrovascular cause was lower in patients who did not undergo DSA, some small arteriovenous malformations or dural arteriovenous fistulas may have been missed., What This Study Adds: CT angiography is an appropriate initial investigation to detect macrovascular causes of non-traumatic intracerebral haemorrhage, but accuracy is modest. Additional MRI/MRA may find cavernomas or alternative diagnoses, but DSA is needed to diagnose macrovascular causes undetected by CT angiography or MRI/MRA., Funding, Competing Interests, Data Sharing: Dutch Heart Foundation and The Netherlands Organisation for Health Research and Development, ZonMw. The authors have no competing interests. Direct requests for additional data to the corresponding author., (© van Asch et al 2015.)

Objective: The objective was to assess the risk of aneurysmal subarachnoid hemorrhage (aSAH) in the initial 15 years after negative aneurysm screening in persons with one first-degree relative with aSAH., Methods: From a cohort of first-degree relatives of patients with aSAH who underwent screening between 1995 and 1997 (n = 626), we included those with a negative screening (n = 601). We retrieved all causes of death and sent a questionnaire to screenees who were still alive. If aSAH was reported, we reviewed all medical data. We assessed the incidence of aSAH in this cohort with survival analysis and calculated an incidence ratio by dividing the observed incidence with the age- and sex-adjusted incidence in the general population., Results: Of the 601 screenees, 3 had aSAH during 8,938 follow-up patient-years (mean 14.9 years). After 15 years, the cumulative incidence was 0.50% (95% confidence interval: 0.00%-1.06%) with an incidence rate of 33.6 per 100,000 person-years; the incidence rate ratio was 1.7 (95% confidence interval: 0.3-5.7)., Conclusions: In the first 15 years after a negative screening, the risk of aSAH in persons with one first-degree relative with aSAH is not nil, but in the range of that in the general population, or even higher. Whether this finding justifies serial aneurysm screening in this population requires further study., (© 2015 American Academy of Neurology.)

Objective: We performed a study in patients with proximal spinal muscular atrophy (SMA) to determine the prevalence of reduced maximal mouth opening (MMO) and its association with dysphagia as a reflection of bulbar dysfunction and visualized the underlying mechanisms using MRI., Methods: We performed a cross-sectional study of MMO in 145 patients with SMA types 1-4 and 119 healthy controls and used MRI in 12 patients to visualize mandibular condylar shape and sliding and the anatomy of muscle groups relevant for mouth opening and closing. We analyzed associations of reduced MMO with SMA severity and complaints of dysphagia., Results: Reduced MMO was defined as an interincisal distance ≤ 35 mm and was found in none of the healthy controls and in 100%, 79%, 50%, and 7% of patients with SMA types 1, 2, 3a, and 3b/4, respectively. MRI showed severe fatty degeneration of the lateral pterygoid muscles that mediate mouth opening by allowing mandibular condylar sliding but relatively mild involvement of the mouth closing muscles in patients with reduced MMO. Reduced MMO was associated with SMA type, age, muscle weakness, and dysphagia (p < 0.05)., Conclusions: Reduced MMO is common in SMA types 1-3a and is mainly caused by fatty degeneration of specific mouth opening muscles. Reduced MMO is a sign of bulbar dysfunction in SMA., (© 2014 American Academy of Neurology.)

Magnetic resonance imaging (MRI) scores for haemophilic arthropathy are useful for evaluation of early and moderate arthropathy. The most recent additive International Prophylaxis Study Group (IPSG) MRI scale for haemophilic arthropathy includes joint effusion. However, it is unknown whether joint effusion is haemophilia specific. Correct interpretation of joint effusion is needed for outcome assessment of prophylactic therapies in haemophilia care. The aim of this study was to compare joint effusion on MRI between young adults with haemophilia and healthy controls. MRI's of both knees and ankles of 26 haemophilic patients (104 joints) and 30 healthy active men (120 joints) were assessed. Scans in both groups were performed in 2009/2010 and 2012 respectively. Joint effusion was measured and scored according to the MRI atlas referred by the IPSG MRI scale for haemophilic arthropathy. Median age of haemophilic patients and healthy controls was 21 and 24 years respectively. In haemophilic patients 23% of knees and 22% of ankles showed joint effusion. Healthy controls had significantly more positive scores for knee effusion (67%, P < 0.01) and a comparable scores for effusion in the ankle (17%). Joint effusion according to criteria of the IPSG MRI scale was observed significantly more often in knees of healthy controls, while findings in ankles were similar. These data suggest that joint effusion in knees and ankles is not haemophilia specific. Inclusion of joint effusion in the MRI scale is expected to reduce its specificity for haemophilic arthropathy., (© 2014 John Wiley & Sons Ltd.)

We estimated the progression of brain atrophy and cerebrovascular lesions on MRI in a prospective cohort of patients with various manifestations of arterial disease. Within the SMART-MR study, using brain MRI data from baseline and after on average 3.9 years of follow-up, intracranial volume (ICV), total brain, cortical gray matter, ventricular, white matter lesion volumes and visually rated infarcts were obtained from 663 patients (mean age 57 ± 9 years, 81% men). Global and cortical atrophy increased quadratically with age. Men showed more progression of global and cortical atrophy than women (mean difference in change (95% CI): -0.25 (-0.44; -0.06) and -0.94 (-1.35; -0.52)% ICV) and had an increased risk of new brain infarcts (OR = 2.7, 95% CI 1.2-6.1). Compared with coronary artery disease patients, cerebrovascular disease patients showed more progression of cortical and subcortical atrophy and an increased risk of new brain infarcts, and peripheral arterial disease patients showed more progression of cortical atrophy. These results were independent of cerebrovascular lesions and cardiovascular risk factors. In patients with manifest arterial disease, brain atrophy tended to accelerate with older age and men had more progression of brain atrophy and cerebrovascular lesions than women. Additionally, patients with cerebrovascular and peripheral arterial disease showed the most prominent progression of atrophy and lesions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Magnetic resonance imaging (MRI) is the most sensitive imaging modality to assess joint lesions, but the clinical relevance of subtle joint changes in haemophilic patients playing sports is unknown. A haemophilia specific MRI score is available, but was never evaluated in physically active healthy controls. It is not known if unexpected MRI changes in young active haemophilic patients are due to sports participation. The aim of this study was to evaluate knees and ankles in a cohort of young active healthy men using a haemophilia specific MRI score to provide context for joint evaluation by MRI in young haemophilic patients. Three Tesla MRI of knees and ankles were performed in 30 healthy men aged 18-26 years, regularly active in sports. MR images were scored by a single independent radiologist, using the International Prophylaxis Study Group additive MRI score. One physiotherapist assessed clinical function using the Haemophilia joint health scores (HJHS). History of complaints or injuries affecting knees and/or ankles, very intensive sports and current sports activities were documented. Median age was 24.3 years (range 19.0-26.4) and median number of sports activities per week was 3 (range 1-4). Six joints (five knees, one ankle) had a history of a sports-related injury. The median HJHS per joint was 0 out of 20 (range 0-1). All joints had a MRI score of 0. These results suggest that regular sports participation or very low HJHS scores are not associated with haemophilia specific MRI changes in knees and ankles., (© 2013 John Wiley & Sons Ltd.)

Although a relation between depression and white matter lesions (WML) is frequently observed, the direction of causation remains unknown. We investigated whether depressed mood was associated with baseline severity and change in WML volume during 4 years of follow-up, and the relative contribution of mood symptoms and antidepressant use to this relation. Within the SMART-MR study 594 patients (58 ± 10 years) with symptomatic atherosclerotic disease had assessments of mood symptoms and antidepressant use and 1.5 T MRI at baseline and after 3.9 ± 0.4 years of follow-up. Mood symptoms were assessed using the Mental Health Index (MHI-5). Depressed mood was defined as antidepressant use and/or MHI-5 score ≤ 52. Volumetric WML measures (deep and periventricular) were obtained with automated segmentation. Linear regression analyses were adjusted for age, sex, baseline WML volume, follow-up time, vascular risk factors and infarcts. Depressed mood was not associated with larger WML volume at baseline. However, when separate contributions were distinguished, antidepressant use was associated with greater deep (B = 0.50 mL, 95 % CI 0.04-0.96) and periventricular WML volume (B = 0.47 mL, 95 % CI 0.05-0.89) at baseline, while mood symptoms were not. Antidepressants were associated with a modest but non-significant increase in progression of periventricular WML volume over 4 years of follow-up (B = 0.21 mL, 95 % CI -0.05 to 0.47). WML at baseline were not associated with new-onset depressed mood at follow-up. Antidepressants, but not mood symptoms, were associated with greater WML volume and a modest, although non-significant increase in periventricular WML volume in patients with symptomatic atherosclerotic disease. Future studies are needed to determine whether this may be a direct effect, or whether other underlying diseases for which antidepressants are prescribed influence this relation.

Background: The 'vascular depression' hypothesis states that brain changes located in frontal-subcortical pathways increase vulnerability for specific depressive symptom profiles, but studies examining locations of small-vessel and degenerative changes with individual symptoms are scarce. We examined whether location and progression of white-matter lesions (WMLs), lacunar infarcts and atrophy were associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease., Method: In 578 patients [63 (s.d.=8) years] of the Second Manifestations of ARTerial disease (SMART)-Medea study, volumes of WMLs and atrophy and visually rated infarcts were obtained with 1.5 T magnetic resonance imaging at baseline and after 3.9 (s.d.=0.4) years' follow-up. Depressive symptoms were assessed with Patient Health Questionnaire-9 at follow-up and categorized into motivational and mood symptoms., Results: Regression analyses adjusted for age, gender, education, Mini-Mental State Examination, physical functioning, antidepressant use and vascular risk factors showed that location in mainly deep white-matter tracts and progression of WMLs were associated with symptoms of anhedonia, concentration problems, psychomotor retardation and appetite disturbance. Lacunar infarcts in deep white matter were associated with greater motivational [Incidence rate ratio (IRR) 1.7, 95% confidence interval (CI) 1.2-2.4] and mood (IRR 1.7, 95% CI 1.1-2.6) sumscores, and with symptoms of psychomotor retardation, energy loss and depressed mood; lacunar infarcts in the thalamus were associated with psychomotor retardation only. Cortical atrophy was associated with symptoms of anhedonia and appetite disturbance. Excluding patients with major depression did not materially change the results., Conclusions: Our findings suggest that disruption of frontal-subcortical pathways by small-vessel lesions leads to a symptom profile that is mainly characteristic of motivational problems, also in the absence of major depression.

Background and Purpose: The detection of microbleeds differs strongly between studies, due to differences in scan protocol. This study aims to compare the visualization of microbleeds with 3D T2*-weighted imaging at 1.5T with 3D dual-echo T2*-weighted imaging at 7T., Materials and Methods: Thirty-four patients (29 male; mean age, 58 ± 12 years) with atherosclerotic disease from the Second Manifestations of ARTerial Disease study were included. 3D T2*-weighted imaging at 1.5T and dual-echo T2*-weighted imaging at 7T were done in all patients. The presence and number of definite microbleeds were recorded on minimal intensity projections. Inter- and intraobserver reliability was assessed with Cohen κ test and the ICC. The difference in presence and number of microbleeds was tested with the McNemar test and Wilcoxon signed rank test., Results: The interobserver ICC at 7T was 0.61 and the intraobserver ICC was 0.94, whereas at 1.5T the interobserver ICC was 0.50 and the intraobserver ICC was 0.59. Microbleeds were detected in significantly more patients on 7T (50%) than on 1.5T scans (21%) (P = .001). The number of microbleeds was also higher at 7T (median, 0.5; range, 0-5) than on 1.5T (median, 0.0; range, 0-6) (P = .002)., Conclusions: 3D dual-echo T2*-weighted imaging at 7T results in better and more reliable detection of microbleeds compared with 3D T2*-weighted imaging at 1.5T.

Objectives. Mechanisms influencing the course of physical and mental functioning after an atherosclerotic event are unclear. We examined effects of white matter lesion (WML) activity on changes in functioning in patients with symptomatic atherosclerotic disease. Methods. In 486 patients (58 ± 9 years) of the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study, volumetric WML measurements on 1.5T MRI were performed at baseline and 3.9 ± 0.4 years followup. Functioning was assessed with the modified Short-Form 12 (SF-12) questionnaire. Associations of WML progression with changes in functioning were adjusted for age, sex, and vascular risk factors. Results. Physical functioning (baseline: 44, 10th-90th percentile 29-55) improved, whereas mental functioning (baseline: 51, 10th-90th percentile 32-60) declined during followup. WML progression (highest quartile versus rest) contributed to a stronger decline in mental functioning (B = -1.76, 95% CI -3.11 to -0.42), but did not influence changes in physical functioning. Conclusions. Progression of WML volume contributes to a decline in mental functioning in patients with symptomatic atherosclerotic disease.

Introduction: This case report describes an extremely rare combination of paroxysmal autonomic instability with dystonia and tuberculous meningitis. Paroxysmal autonomic instability with dystonia is normally associated with severe traumatic brain injury., Case Presentation: A 69-year-old man of Indonesian descent was initially suspected of having a community-acquired pneumonia, which was seen on chest X-ray and computed tomography of the chest. However, a bronchoscopy showed no abnormalities. He was treated with amoxicillin-clavulanic acid in combination with ciprofloxacin. However, nine days after admission he was disorientated and complained of headache. Neurological examination revealed no further abnormalities. A lumbar puncture revealed no evidence of meningitis. He was then transferred to our hospital. At that time, initial cultures of bronchial fluid for Mycobacterium tuberculosis turned positive, as well as polymerase chain reaction for Mycobacterium tuberculosis. Later, during his stay in our intensive care unit, he developed periods with hypertension, sinus tachycardia, excessive transpiration, decreased oxygen saturation with tachypnea, pink foamy sputum, and high fever. This constellation of symptoms was accompanied by dystonia in the first days. These episodes lasted approximately 30 minutes and improved after administration of morphine, benzodiazepines or clonidine. Magnetic resonance imaging showed an abnormal signal in the region of the hippocampus, thalamus and the anterior parts of the lentiform nucleus and caudate nucleus., Conclusions: In patients with (tuberculous) meningitis and episodes of extreme hypertension and fever, paroxysmal autonomic instability with dystonia should be considered.

Purpose: To determine the test characteristics of magnetic resonance (MR) angiography in the assessment of occlusion of aneurysms treated with coil placement., Materials and Methods: This was an ethics committee-approved multicenter study. written informed consent was obtained in 311 patients with 343 aneurysms, who had been treated with coil placement and were scheduled for routine follow-up with intraarterial digital subtraction angiography (DSA). Thirty-five patients participated two or three times. Either 3.0- or 1.5-T time-of-flight (TOF) and contrast material-enhanced MR angiography were performed in addition to intraarterial DSA. Aneurysm occlusion was evaluated by independent readers at DSA and MR angiography. The test characteristics of MR angiography were assessed by using DSA as the standard. The area under the receiver operating characteristic curve (AUC) was calculated for 3.0- versus 1.5-T MR angiography and for TOF versus contrast-enhanced MR angiography, and factors associated with discrepancies between MR angiography and DSA were assessed with logistic regression., Results: Aneurysm assessments (n = 381) at DSA and MR angiography were compared. Incomplete occlusion was seen at DSA in 88 aneurysms (23%). Negative predictive value of MR angiography was 94% (95% confidence interval [CI]: 91%, 97%), positive predictive value was 69% (95% CI: 60%, 78%), sensitivity was 82% (95% CI: 72%, 89%), and specificity was 89% (95% CI: 85%, 93%). AUCs were similar for 3.0- (0.90 [95% CI: 0.86, 0.94]) and 1.5-T MR (0.87 [95% CI: 0.78, 0.95]) and for TOF MR (0.86 [95% CI: 0.81, 0.91]) versus contrast-enhanced MR (0.85 [95% CI: 0.80, 0.91]). A small residual lumen (odds ratio, 2.1 [95% CI: 1.1, 4.3]) and suboptimal projection at DSA (odds ratio, 5.5 [95% CI: 1.5, 21.0]) were independently associated with discordance between intraarterial DSA and MR angiography., Conclusion: Documentation of good diagnostic performance of TOF MR angiography at both 1.5 and 3.0 T in the current study represents an important step toward replacing intraarterial DSA with MR angiography in the follow-up of patients with aneurysms treated with coils.

Objective: To estimate brain volumes, white matter lesion (WML) volume and asymptomatic infarcts on MRI in a large cohort of patients with atherosclerotic disease., Methods: Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) study, a prospective cohort study on determinants and course of brain changes on MRI, cross-sectional analyses were performed in 1044 patients (mean age 58+/-10 years, 80% male) with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm. Brain segmentation was used to quantify volumes of cortical gray matter, white matter, sulcal and ventricular cerebrospinal fluid, and WML. All volumes were expressed relative to intracranial volume. Brain infarcts were rated visually and distinctions were made between cortical infarcts, large subcortical infarcts, lacunar infarcts, and infarcts in the cerebellum and brainstem., Results: With older age a nonlinear (quadratic) decrease in total brain volume was observed and a nonlinear increase in ventricular volume and WML. Cortical gray matter volume showed a linear decrease with age and was stronger in men than in women. WML volumes also increased more strongly in men than in women, while ventricular volume decrease showed no sex difference. Silent brain infarcts were present in 14% of men and women, and increased to 24% of subjects aged 65 years or older., Conclusion: In a population with atherosclerotic diseases, decrease in brain volumes with increasing age is comparable with findings from the general population. However, vascular pathology on MRI, as indicated by white matter lesions and silent brain infarcts may be more common., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI., Methods: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 +/- 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually., Results: Mean +/- SD BPF was 79.3 +/- 2.8%, mean +/- SD VF was 2.01 +/- 0.95%, and mean +/- SD GMF was 36.6 +/- 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (-0.51%; 95% CI -0.93 to -0.08%), VF was higher (0.48%; 95% CI 0.31-0.65%) and GMF was lower (-1.48%; 95% CI -2.07 to -0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (-0.52%; 95% CI -0.96 to -0.07%) and higher VF (0.25%; 95% CI 0.07-0.42%), but not with GMF, independent of WML and other potential confounders., Conclusion: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

White matter lesions (WML) are a frequent finding on brain magnetic resonance imaging scans. Elevated blood pressure (BP) is consistently identified as risk factor for WML. However, it is unknown whether BP still is associated with WML in patients with manifest vascular disease. The aim of this cross-sectional study was to investigate associations between BP and WML in patients with manifest vascular disease. A total of 1030 patients with vascular disease (cerebrovascular disease (23%), coronary heart disease (59%), peripheral arterial disease (23%), abdominal aortic aneurysm (9%)) from the Second Manifestations of Arterial Disease study were included. WML volume was calculated using an automated quantitative volumetric method and subsequently divided into quartiles. We investigated associations between BP and WML and examined whether relations between BP and WML were modified by the localization of the symptomatic site or presence of diabetes. Participants had a mean age of 58.7 years. Median volume of WML was 1.70 ml. Mean BP was 141/82 mmHg and 69% suffered hypertension. No significant associations between systolic BP, diastolic BP, mean arterial pressure (MAP) or hypertension presence and moderate or large WML volumes were present. The relation between BP and WML was not modified by the localization of vascular disease or diabetes presence. Among patients with manifest vascular disease, BP was not associated with the presence of WML, irrespective of the presence of diabetes or the localization of vascular disease.

Purpose: To study 3T compared to 1.5T phased array magnetic resonance imaging (MRI) in the presurgical work-up of patients with epilepsy with complex focus localization., Materials and Methods: In all, 37 patients (>10 years) in preoperative work-up for epilepsy surgery were offered 3T in addition to 1.5T MRI if ambiguity existed about the epileptic focus. Scans were randomly reviewed by two observers, blinded for prior imaging, patient-identifying information, and each other's assessments, followed by a consensus meeting. The number of abnormal scans, detected lesions, and interobserver agreement were calculated and compared. The final consensus was compared to original scan reports., Results: One observer identified 22 lesions in both 3 and 1.5T scans, while the second identified more lesions in 1.5T scans (28 vs. 20). 3T MRI had better interobserver agreement. 3T revealed more dysplasias, while 1.5T revealed more tissue loss and mesial temporal sclerosis (MTS). The final consensus yielded 29 lesions, whereas original reports identified only 17 lesions., Conclusion: The 3T scans revealed different lesions compared to 1.5T. Patients can benefit most from 3T scans when a dysplasia is suspected. Reevaluation by another experienced neuroradiologist is advised in case of negative or equivocal MRIs., ((c) 2009 Wiley-Liss, Inc.)

Objective: To report the presence of intracerebral hemorrhage and porencephaly, both present at birth, in two preterm infants with a mutation in the collagen 4 A1 gene., Methods: Two preterm infants with antenatal intracerebral hemorrhage and established porencephaly, as well as their affected mother and grandfather, underwent neurological and ophthalmological examination and magnetic resonance imaging of the brain. Mutation analysis of the COL4A1 gene was performed in the infants and in their mother., Results: Both infants had a novel G1580R mutation in the COL4A1 gene, encoding procollagen type IV alpha1. A history of mild antenatal trauma was present in the first but not in the second infant. Both preterm infants were asymptomatic at birth. The intracerebral hemorrhage and porencephaly were diagnosed with cranial ultrasound examination and were subsequently confirmed with magnetic resonance imaging. Leukoencephalopathy was present in the mother and in her father., Interpretation: Mutation of the COL4A1 gene appears to be a risk factor of antenatal intracerebral hemorrhage followed by porencephaly in the preterm newborn.

The authors present the case of a 4-year-old boy in whom a medulloblastoma in the left cerebellar hemisphere was successfully resected with no signs of residual tumor on the postoperative magnetic resonance (MR) images. A second MR imaging study performed 1 month after surgery demonstrated an extensive, contrast-enhancing lesion in the left cerebellar hemisphere, which simulated massive recurrent tumor, and repeated surgery was considered. A third postoperative MR imaging study, performed for evaluation of the craniospinal axis 10 days after the second postoperative study, still showed some contrast enhancement in the left cerebellar hemisphere, but the lesion had almost disappeared. Postoperative hemicerebellar inflammation seemed to be the most likely explanation. This case illustrates that early postoperative inflammation can mimic recurrent tumor on MR images obtained after resection of a medulloblastoma and caution should be taken in interpreting such images. Clinical history, neurological examination, laboratory findings, and repeated MR imaging studies can be helpful in evaluating the patient accurately.

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58+/-10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0+/-10.2 mL/min per 100 mL, mean BPF was 79.2+/-2.9%, and mean VF was 2.03+/-0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.

Purpose: To evaluate whether magnetic-resonance (MR) sialography can be used to investigate radiation-induced xerostomia. Preradiotherapy (pre-RT) and postradiotherapy (post-RT) MR sialographic images of the major salivary ducts (parotid and submandibular) were compared., Methods and Materials: Magnetic-resonance sialography was performed pre-RT, and 6 weeks and 6 months post-RT on 9 patients with T1-4N0-2M0 naso- or oropharyngeal tumors, on a 1.5-T MR scanner. Patients were positioned in the scanner, using a radiotherapy immobilization mask. Image registration of the MR sialograms pre- and post-RT with each other and with the CT and consequently the dose distribution was performed. A categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT., Results: Good-quality MR sialographic images were obtained, and image registration was successful in all cases. The visibility score of the parotid ducts and submandibular ducts was reduced at 6 weeks post-RT, which means that the full trajectory of the salivary ducts, from the intraglandular space to the mouth cavity, was only partially visualized. For some of the parotid ducts, the visibility score improved at 6 months post-RT, but not for the submandibular ducts. The mean dose for the parotid glands was 35 Gy (1 standard deviation [SD] 3 Gy), and for the submandibular glands it was 62 Gy (SD, 8 Gy)., Conclusion: Three-dimensional MR sialography is a promising approach for investigating xerostomia, because radiation-induced changes to the saliva content of the ducts can be visualized.

Objectives: We sought to confirm earlier findings in the literature that microvascular compression of the vestibulocochlear nerve might cause unilateral sensorineural hearing loss. We measured the length and width of the internal auditory canal (IAC) to investigate a possible association between a narrow porus, the presence of an anterior inferior cerebellar artery (AICA) loop, and the development of a microvascular compression syndrome., Methods: We performed a prospective blinded analysis of 167 magnetic resonance imaging scans of the cerebellopontine angle. The presence of an AICA loop was scored. We analyzed these 167 patients for unilateral sensorineural hearing loss, which was defined as an interaural difference of 20 dB at 1 frequency or 10 dB at 2 or more frequencies. Furthermore, the width and length of the IAC on magnetic resonance imaging were measured., Results: An AICA loop was identified in 94% of the 167 patients. There were 196 type I loops, 106 type II loops, and 14 type III loops. Sixty-six patients had unexplained unilateral hearing loss. There was no association between type II and III vascular loops, the width of the IAC, and unilateral hearing loss (p > .05)., Conclusions: In this study we found no association between the depth of extension of the AICA loop into the IAC and the presence of unilateral hearing loss.

Object: Multislice computed tomography (CT) angiography may be useful for screening patients with intracranial aneurysms that are treated with clip occlusion. However, cobalt clips produce much more artifact on CT scans than titanium clips, which may hamper the evaluation of the image obtained at the clip site., Methods: The authors screened 415 patients with previously ruptured aneurysms that had been treated using cobalt clips. Screening was performed using multislice CT angiography. The feasibility of this modality for screening these patients (based on the complication risk, CT angiography quality, and artifact avoidance) and interobserver agreement were evaluated. Patients in whom the presence of an aneurysm was suspected based on results of CT angiography studies underwent digital subtraction (DS) angiography. False-negative and false-positive findings were recorded, and the positive predictive value (PPV) was calculated. Eight patients (1.9%) had allergies to the contrast material. The quality of the CT angiography image was suboptimal in 14%. In 52%, clip artifacts hampered evaluation of the clip site. In 65 patients who underwent DS angiography, there were nine false-positive and eight false-negative reports related to aneurysms that were either small, located at the clip site, or were infundibula. The PPV on a per-patient basis was 86% (95% confidence interval [CI] 75-94%); for aneurysms at the clip site it was 83% (95% CI 61-95%); and for aneurysms at different locations it was 91% (95% CI 81-97%). The interobserver agreement was good (kappa = 0.69; 95% CI 0.60-0.78)., Conclusions: Except for the evaluation of images from the clip site, CT angiography has good feasibility with good PPV and interobserver agreement. Drawbacks are that very small aneurysms can be missed and that visualization is poor at the clip site in patients in whom cobalt clips have been placed for occlusion. This second problem can be expected to resolve with the increasing use of titanium clips.

Purpose: To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities., Materials and Methods: MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers., Results: MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume., Conclusion: This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.