Decline in total cerebral blood flow is linked with increase in periventricular but not deep white matter hyperintensities

PURPOSE: To retrospectively investigate the association between changes in total cerebral blood flow and progression of total, periventricular, and deep white matter hyperintensities over time. MATERIALS AND METHODS: The institutional ethics review board approved the protocol for the prospective magnetic resonance (MR) imaging study, and all participants gave written informed consent. Participants also agreed to future retrospective analysis of their MR data for research purposes. In this substudy of the Prospective Study of Pravastatin in the Elderly at Risk, investigators performed a repeated MR imaging examination after an average interval of 33 months (standard deviation, 1.4) in 390 elderly men and women (ages 70-82 years at baseline) without dementia who were at high vascular risk. White matter hyperintensities were quantified with a semiautomatic method, and total cerebral blood flow was measured with a gradient-echo phase-contrast MR imaging technique. The association between total cerebral blood flow and volume of white matter hyperintensities was analyzed with logistic regression. RESULTS: There was no association between baseline cerebral blood flow and prevalence of total, periventricular, or deep white matter hyperintensities at baseline MR imaging. Moreover, decline in cerebral blood flow was not associated with increase in total load of white matter hyperintensities. When the total volume of white matter hyperintensities was separated into periventricular and deep hyperintensities, for every 50 mL/min decrease in total cerebral blood flow there was a 1.32 (95% confidence interval: 1.06, 1.66; P = .015) increase in risk for developing periventricular white matter hyperintensities; there was no association, however, between decrease in total cerebral blood flow and risk of developing deep white matter hyperintensities (odds ratio, 1.00 [95% confidence interval: 0.79, 1.25]; P = .98). CONCLUSION: Decline in total cerebral blood flow is associated with increase in volume of periventricular but not deep white matter hyperintensities.     

TGFβ pathway deregulation and abnormal phospho‐SMAD2/3 staining in hereditary cerebral hemorrhage with amyloidosis‐Dutch type

Hereditary cerebral hemorrhage with amyloidosis‐Dutch type (HCHWA‐D) is an early onset hereditary form of cerebral amyloid angiopathy (CAA) pathology, caused by the E22Q mutation in the amyloid β (Aβ) peptide. Transforming growth factor β1 (TGFβ1) is a key player in vascular fibrosis and in the formation of angiopathic vessels in transgenic mice. Therefore, we investigated whether the TGFβ pathway is involved in HCHWA‐D pathogenesis in human postmortem brain tissue from frontal and occipital lobes. Components of the TGFβ pathway were analyzed with quantitative RT‐PCR. TGFβ1 and TGFβ Receptor 2 (TGFBR2) gene expression levels were significantly increased in HCHWA‐D in comparison to the controls, in both frontal and occipital lobes. TGFβ‐induced pro‐fibrotic target genes were also upregulated. We further assessed pathway activation by detecting phospho‐SMAD2/3 (pSMAD2/3), a direct TGFβ down‐stream signaling mediator, using immunohistochemistry. We found abnormal pSMAD2/3 granular deposits specifically on HCHWA‐D angiopathic frontal and occipital vessels. We graded pSMAD2/3 accumulation in angiopathic vessels and found a positive correlation with the CAA load independent of the brain area. We also observed pSMAD2/3 granules in a halo surrounding occipital vessels, which was specific for HCHWA‐D. The result of this study indicates an upregulation of TGFβ1 in HCHWA‐D, as was found previously in AD with CAA pathology. We discuss the possible origins and implications of the TGFβ pathway deregulation in the microvasculature in HCHWA‐D. These findings identify the TGFβ pathway as a potential biomarker of disease progression and a possible target of therapeutic intervention in HCHWA‐D.     

Memory activation enhances EEG abnormality in mild cognitive impairment

This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions ('eyes closed' and 'eyes open') and three memory conditions ('word memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to 'eyes closed'. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not.     

Management of rhinosinusitis in children

The authors provide definitions for the different forms of pediatric rhinosinusitis, with an enumeration of the main symptoms and signs. They also provide the indications for CT scan examination and microbiological investigations. In addition, they emphasize the importance of concomitant systemic disease, such as allergy and immunological disorders. The adequate medical management, which is mandatory before any surgery, is considered and discussed, and the indications for surgery are provided.     

Magnetization transfer: applications in neuroradiology

Magnetization transfer imaging is a technique that was introduced into clinical radiology in the early nineteen nineties and which has gained in popularity ever since, particularly in the field of neuroradiology. This paper presents an overview of the clinical and scientific applications of magnetization transfer imaging in neuroradiology.     

Neuropsychological correlates of MRI measures in the continuum of cognitive decline at old age

OBJECTIVE: To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20 patients with mild cognitive impairment and 28 elderly subjects without memory complaints were assessed using a neuropsychological test battery. Quantitative MRI measures of medial temporal lobe volume and WMH were obtained. Multiple regression analyses were performed to assess the independent contribution of MRI measures to impairment in several cognitive functions. RESULTS: Scores on the Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe volume, whereas WMH selectively contributed to performance on Trails A. Medial temporal lobe volume and WMH both contributed to scores on the Cambridge Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures suggestive of Alzheimer-type pathology and microvascular pathology independently contribute to cognitive decline at old age. Memory impairment as measured using the Wechsler Memory Scale and performance on Trails B primarily depended on medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A, mainly depended on WMH. These results suggest that vascular pathology and Alzheimer-type pathology each have specific cognitive correlates.     

Age-related changes in normal-appearing brain tissue and white matter hyperintensities: more of the same or something else?

BACKGROUND AND PURPOSE: Cerebral white matter (WM) hyperintensities are a frequent finding in elderly people, and lowering of cerebral magnetization transfer ratio (MTR) has been observed. The aim of this study was to assess the relationship between age-related WM hyperintensities and MTR changes in the brain. METHODS: We performed MR imaging in a group of young subjects, a group of elderly individuals with minimal WM hyperintensities, and a group of elderly individuals with abundant WM hyperintensities. In addition, we performed volumetric MTR analysis of the whole brain and of the normal-appearing WM (NAWM) in these groups. RESULTS: Volumetric MTR parameters differed between elderly and young patients. Mean MTR +/- standard error of the mean (SEM) was 34.0% +/- 0.12% in the young, 33.0% +/- 0.08% in the elderly with minimal WM hyperintensities, 32.8% +/- 0.09%) in the group with abundant WM hyperintensities. Peak height (number of voxels +/- SEM) was 122 +/- 1.2 in the young, 99 +/- 1.5 in the elderly with minimal WM hyperintensities, and 98 +/- 1.6 in the group with abundant WM hyperintensities. Mean MTR of NAWM was lower in the elderly compared with the young (36.7% +/- 0.12%) but did not differ between subjects with minimal (36.0% +/- 0.11%) and those with abundant WM hyperintensities (35.9% +/- 0.13%). CONCLUSION: Our results show that aging gives rise to changes in normal-appearing brain tissue. These changes, which can be detected on magnetization transfer imaging, seem to have no relationship with age-related WM hyperintensities and might have a different etiology.