Areas Of White Matter Hyperintensity Research Articles

Unusual Predominant Memory Decline in an Early-Stage CADASIL Patient: A Four-Year Longitudinal Follow-Up of Hereditary Vascular Dementia

Introduction: Deficits in executive function and processing speed have traditionally been viewed as the chief cognitive manifestation of vascular contributions to cognitive impairment and dementia. This case study describes the longitudinal progression of cognitive symptoms in a 42-year-old Colombian woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary condition leading to the early onset of cerebral small vessel disease. Because of the young age of onset of vascular cognitive impairment, CADASIL allows examining the early cognitive consequences of cerebrovascular changes in the absence of age-related comorbidities. Methods: We followed the neuropsychological progression of a non-demented and stroke-free patient carrying a CADASIL mutation, in parallel to that of 13 non-carrier control subjects. At baseline, all subjects completed detailed clinical, neurological, and neuropsychological evaluations as well as an MRI scan. After a period of four years, subjects completed a follow-up neuropsychological evaluation. Results: Examination of the patient’s baseline MRI revealed the presence of significant areas of white matter hyperintensity. The patient did not present cerebral microbleeds, lacunes, notable brain atrophy, or evidence of previous strokes. In contrast to non-carrier subjects, the patient experienced predominant memory decline, with relatively preserved executive function and processing speed. Conclusions: This case highlights the heterogeneity of cognitive deficits associated with cerebrovascular disease.

Identifying microstructural changes in diffusion MRI; How to circumvent parameter degeneracy

Biophysical models that attempt to infer real-world quantities from data usually have many free parameters. This over-parameterisation can result in degeneracies in model inversion and render parameter estimation ill-posed. However, in many applications, we are not interested in quantifying the parameters per se, but rather in identifying changes in parameters between experimental conditions (e.g. patients vs controls). Here we present a Bayesian framework to make inference on changes in the parameters of biophysical models even when model inversion is degenerate, which we refer to as Bayesian EstimatioN of CHange (BENCH).We infer the parameter changes in two steps; First, we train models that can estimate the pattern of change in the measurements given any hypothetical direction of change in the parameters using simulations. Next, for any pair of real data sets, we use these pre-trained models to estimate the probability that an observed difference in the data can be explained by each model of change.BENCH is applicable to any type of data and models and particularly useful for biophysical models with parameter degeneracies, where we can assume the change is sparse. In this paper, we apply the approach in the context of microstructural modelling of diffusion MRI data, where the models are usually over-parameterised and not invertible without injecting strong assumptions. Using simulations, we show that in the context of the standard model of white matter our approach is able to identify changes in microstructural parameters from conventional multi-shell diffusion MRI data. We also apply our approach to a subset of subjects from the UK-Biobank Imaging to identify the dominant standard model parameter change in areas of white matter hyperintensities under the assumption that the standard model holds in white matter hyperintensities.

Slowing: A Vascular Geriatric Syndrome?

This study aimed to investigate the interrelation between slowing in walking, thinking and mood, and their relationship with cerebral small vessel disease (CSVD) in a geriatric population. Cross-sectional study. 566 geriatric outpatients from the Amsterdam Aging Cohort (49% female; age 79 ±6years), who visited the Amsterdam UMC geriatric outpatient memory clinic. Patients underwent a comprehensive geriatric assessment, brain imaging, and a neuropsychological assessment as part of medical care. Three slowing aspects were investigated: gait speed, processing speed, and apathy symptoms (higher scores indicating more advanced slowing). We visually rated CSVD [white matter hyperintensities (WMHs), strategic lacunes, and microbleeds] on brain imaging. Regression analyses showed that slowing in walking (gait speed) was associated with slowing in thinking [processing speed; β= 0.35, 95% confidence interval (CI) 0.22, 0.48] and slowing in mood (apathy symptoms; β= 0.21, 95% CI 0.13, 0.30), independent of important confounders. Large confluent areas of WMH (Fazekas 3) were associated with all slowing aspects: gait speed (β= 0.49, 95% CI 0.28, 0.71), processing speed (β= 0.36, 95% CI 0.19, 0.52) and apathy symptoms (β= 0.30, 95% CI 0.09, 0.51). In addition, in patients with more slowing aspects below predefined cutoffs, severe WMH was more common. Presence of ≥3 microbleeds was associated with apathy symptoms (β= 0.39, 95% CI 0.12, 0.66), whereas lacunes were not associated with slowing. This study provides evidence that slowing in walking, thinking, and mood are closely related and associated with CSVD. This phenotype or geriatric syndrome could be helpful to identify and characterize patients with CSVD.

White matter hyperintensities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer\u2019s disease

BackgroundWe aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD).MethodsAutopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick’s] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group.ResultsBurden and regional distribution of WMH differed significantly between neuropathological groups (F5,77 = 2.67, P’ = 0.029), with the FTLD-TDP group having the highest mean volume globally (8032 ± 8889 mm3) and in frontal regions (4897 ± 6163 mm3). The AD group had the highest mean volume in occipital regions (468 ± 420 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy.ConclusionsThese findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia

White matter hyperintensities (WMH) occur in association with dementia but the aetiology is unclear. Here we test the hypothesis that there is a combination of impaired elimination of interstitial fluid from the white matter together with a degree of hypoxia in WMH. One of the mechanisms for the elimination of amyloid-β (Aβ) from the brain is along the basement membranes in the walls of capillaries and arteries (Intramural Peri-Arterial Drainage – IPAD). We compared the dynamics of IPAD in the grey matter of the hippocampus and in the white matter of the corpus callosum in 10 week old C57/B16 mice by injecting soluble Aβ as a tracer. The dynamics of IPAD in the white matter were significantly slower compared with the grey matter and this was associated with a lower density of capillaries in the white matter. Exposing cultures of smooth muscle cells to hypercapnia as a model of cerebral hypoperfusion resulted in a reduction in fibronectin and an increase in laminin in the extracellular matrix. Similar changes were detected in the white matter in human WMH suggesting that hypercapnia/hypoxia may play a role in WMH. Employing therapies to enhance both IPAD and blood flow in the white matter may reduce WMH in patients with dementia.

Areas of white matter hyperintensities and motor symptoms of Parkinson disease.

To determine whether deep white matter and periventricular hyperintensities affect the motor symptoms of Parkinson disease (PD) differently, we analyzed MRI and dopamine transporter imaging. We analyzed the medical records of patients with de novo PD who underwent dopamine transporter PET scanning and MRI at their first visit. Deep white matter and periventricular hyperintensities were scored with a visual rating scale, and motor symptoms were assessed by Unified Parkinson's Disease Rating Scale motor score and tremor, rigidity, bradykinesia, and axial symptom subscores. The influence of white matter hyperintensity on motor symptoms was explored using multivariable linear regression models. A total of 93 patients (mean age, 67.2 ± 9.9 years; 44 male) were included and the mean motor score was 25.0 ± 10.8. Subscores for bradykinesia and axial symptoms were correlated with both deep white matter and periventricular hyperintensities scores. Multivariable linear regression models revealed that deep white matter hyperintensities score was significantly associated with subscore for bradykinesia and periventricular hyperintensities score was associated with subscores for bradykinesia and axial symptoms after adjusting for putaminal dopamine transporter availability and clinical factors. These results demonstrate that deep white matter hyperintensities are associated with bradykinesia and periventricular hyperintensities are associated with bradykinesia and axial symptoms in patients with PD independently of the severity of dopaminergic depletion.

Remote brain hemorrhage after IV thrombolysis: Role of preexisting lesions.

To test the hypothesis that remote intracerebral hemorrhages (r-ICHs) after IV thrombolysis occur in preexisting brain lesions. We prospectively collected baseline data from consecutive patients treated with IV thrombolysis for cerebral ischemia and reviewed their baseline MRI scans to identify preexisting lesions in those who developed r-ICH. We evaluated outcomes with the modified Rankin Scale (mRS) and defined good outcomes as scores of 0 to 2 or similar to the preexisting mRS score. Of 944 patients, 24 (2.5%) had r-ICH: lobar in 14, deep in 7, and both in 3. Sixteen of them (1.7% of all patients, 66.7% of those with r-ICH) were asymptomatic. Of the 41 r-ICHs found in these patients, 17 (41%) occurred within a lesion present before thrombolysis: 6 cerebral microbleeds (CMBs), 6 old and 1 recent infarct, and 4 areas of white matter hyperintensity. Patients with r-ICH were more likely to have strictly lobar CMBs (p = 0.049). They were 10 years older (p = 0.007), had a 16-mm Hg higher systolic blood pressure (p = 0.035) at baseline, and had more CMBs (p = 0.007). r-ICHs were better predicted by clinical (age, baseline systolic blood pressure) than imaging (purely lobar CMBs and having >5 CMBs) variables. r-ICHs tended to be associated with worse outcomes. We identified preexisting brain lesions in nearly half of the patients with r-ICH. All were of vascular origin, supporting the hypothesis that r-ICHs occur in preexisting brain lesions. Higher-field machines could help identifying preexisting lesions in those who developed r-ICH in an apparently normal area.

BLOOD PRESSURE AND BLOOD GLUCOSE ARE ASSOCIATED WITH MYELIN VULNERABILITY IN AN ETHNICALLY DIVERSE SAMPLE OF OLDER ADULTS

Hypertension and Type 2 diabetes are cardiovascular disease risk factors (CVD-RFs) associated with pathological aging, including Alzheimer's disease (AD) and vascular dementia. Mid-life hypertension and diabetes predict late-life white matter alterations including white matter hyperintensities (WMH) associated with dementia. Further, evidence suggests that these CVD-RFs may exert their impact as early as the third or fourth decade of life in affected individuals. Hypertension and diabetes are two of the most prevalent CVD-RFs in minority populations, and rates of treatment-related control in these populations lag behind those of non-Hispanic Whites. Work is needed to detect white matter vulnerability associated with CVD-RFs before overt damage occurs. Given that myelin degradation is thought to contribute to white matter damage, we focused this study on multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) as it relates to CVD-RFs in an ethnically diverse sample of older adults. Forty-six non-demented/non-depressed participants (mean age=66.4 years; 56% female; equal % Black/Hispanic/non-Hispanic White) underwent 3T MRI. mcDESPOT quantified ‘restricted’ water trapped within the lipid bilayers of myelin sheath, providing a measure of myelin water fraction (MWF). Regardless of medication status, systolic blood pressure (SBP) was determined via two readings separated by 5-minute intervals; blood glucose was measured by fasting levels of hemoglobin A1c. Separate age-adjusted linear regressions investigated the associations between SBP and A1c on whole-brain MWF. Analyses were fully corrected for multiple comparisons and utilized threshold-free cluster enhancement. Higher SBP was associated with lower MWF within deep white matter and parietal regions (p<.05), whereas greater A1c was associated with lower MWF in deep white matter and more temporal regions (p<.05; see Figure 1a). Similar associations were noted in a subset of fifteen Hispanics at increased risk for uncontrolled CVD-RFs (see Figure 1b). Higher levels of SBP and A1c are associated with decreased myelin integrity in a sample of older, ethnically diverse adults. These results suggest that mcDESPOT may be a useful tool to detect the adverse effects of CVD-RFs on white matter integrity in and around areas of WMH in older non-demented/non-depressed adults. Age-adjusted associates of myelin water fraction with systolic blood pressure (red) and fasting blood glucose (blue) fully corrected for multiple comparisons: Threshold-Free Cluster Enhancement p<.05 in 46 adults (a) and 15 Hispanics (b).

Hyperinsulinemia and elevated systolic blood pressure independently predict white matter hyperintensities with associated cognitive decrement in the middle-aged offspring of dementia patients.

Cerebrovascular disease is an independent risk factor for dementia that may also be synergistic with Alzheimer's disease. In recent years attention has switched from cerebral infarcts to microvascular disease as the primary cause of cerebrovascular cognitive decline, with damage to the white matter the primary mechanism. Uncertainties remain regarding the risks posed by different types vascular threat, the extent to which cerebrovascular damage occurs in middle age, and whether relatively "normal" amounts of white matter damage are accompanied by meaningful degrees of cognitive decline. We explored these issues via laboratory, cardiovascular, cognitive, and magnetic resonance imaging (MRI) data in 67 middle-aged cognitively normal offspring of dementia patients. The sample was enriched for vascular risk. Plasma insulin, 24-h systolic blood pressure, body mass index, age, and % small dense LDL cholesterol were the strongest correlates of MRI white matter hyperintensity (WMH) volume. With shared variance controlled for, 24h systolic BP, plasma insulin, and age remained as significant predictors of WMH volume. An interaction variable (24h BP * insulin) did not improve the prediction of WMH. WMH volume correlated negatively with cognition. No evidence for an ApoE ε4 effect emerged for either WMH or cognition. Hypertension and hyperinsulinemia appear to pose independent, consequential threats to the cerebral small vessel vasculature in middle age, reflected in the presence of areas of WMH on MRI scans. Our data show that even modest WMH volumes in middle age are associated with cognitive decrement, underscoring the importance of aggressive treatment and lifestyle modifications to address vascular risk throughout adulthood.

White Matter Microstructural Damage on Diffusion Tensor Imaging in Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) is a major health problem for its contribution to ≈45% of dementias, and about a fifth of all strokes worldwide, representing one of the most important causes of disabilities.1 The term SVD refers to a group of pathological processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. The most common forms are age- and hypertension-related SVD and cerebral amyloid angiopathy (CAA).2 Vessel wall changes may lead to both ischemic and hemorrhagic consequences: (1) a state of chronic hypoperfusion or vascular dysfunction responsible for incomplete infarction,3,4 (2) acute focal necrosis (lacunar infarct), or (3) vessel rupture manifesting as hemorrhagic SVD. The clinical consequences of SVD are various and mainly consist of cognitive, mood, and motor dysfunctions leading to functional disability in the late stages of the disease. Magnetic resonance imaging (MRI) has become crucial in the diagnosis of SVD enabling the evaluation of the disease progression both in the clinical and research settings. However, correlations between clinical features of SVD and conventional MRI measures have been partially discordant. Some authors suggested that the cumulative effect of SVD lesions, rather than the individual lesions themselves determines the clinical impact,5 whereas others suggested that the presence and severity of alterations nonvisible on conventional MRI might also be an explanation.6 In the past decade, diffusion tensor imaging (DTI) has been increasingly used for the evaluation of SVD patients because it is sensitive to tissue damage and can show abnormalities in both areas of white matter hyperintensities (WMH) and in normal appearing WM (NAWM). Despite the high sensitivity in detecting cerebral damage, DTI has a low specificity in detecting the underlying cause. In fact, we can only infer that DTI changes reflect a loss of WM …

PP08.13 – 2590: Unusual initial presentation of multiple sclerosis

Objective We report a 14 years old boy and a 17 years old girl with tonic spasms (TS) as first manifestation of multiple sclerosis (MS). This is the first report in which TS occured as first manifestations of demyelinating disease in pediatric population. Case report The first patient was a 14-year-old boy with MS diagnosed 14 months after he presented daily several short TS involving the left limbs and the left side of his face. The neurological examination was otherwise unremarkable. Brain MRI revealed areas of T2 abnormality in periventricular frontal white matter, right internal capsule and right corona radiata. These events spontaneously disappeared after 3 weeks. The second patient was a 17-year-old girl who presented brief episodes of TS involving right upper limb and the right hemiface. The brain MRI showed multiple areas of white matter hyperintensity, icluding lesion in the left cerebral peduncle. TS spontaneously disappeared after 2 months. In both cases TS were triggered reliably by hyperventilation. Conclusion Tonic spasms are the most common form of involuntary movements in MS, occuring in 3.8 to 17% of these patients. The seizure-like, involuntary dystonic spasms may be unilateral or bilateral and, in certain occasions, are triggered by voluntary movements, sensory stimulation, hyperventilation or emotions. They usually occur several times a day and last up to 2 minutes. TS have a stereotypical course and can be chronic or recurrent, with repeated episodes every several days or months. MRI frequently shows lesions in the areas of basal ganglia, internal capsule, cerebral peduncles, medulla and spinal cord. TS result from axonal activation secondary to ephaptic cross-transmission in the demyelinated plaques at any level of the motor path. We report these cases to raise awareness of this under-recognized aspect of transient neurologic events during MS.

Intracisternal cyclodextrin ameliorates neurological dysfunction, increases survival time, and stops Purkinje cell death in feline Niemann–Pick type C1 disease

Mucopolysaccharidosis IIIB (MPS IIIB; Sanfilippo syndrome type B) is an autosomal recessive lysosomal disorder caused by a marked decrease in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity which leads to the build-up of abnormal amounts of heparan sulfate (HS) in the brain and other organs. At present there is no treatment for this disorder. Recent scientific studies have indicated a possible defect in the blood–brain barrier (BBB) in mice with MPS IIIB and in patients withMPS IIIA and IIID. A detailed study of the nature and integrity of the BBB is crucial to understand the pathogenesis of structural and functional brain abnormalities in MPS IIIB patients. We evaluated BBB integrity and structural brain abnormalities in MPS IIIB patients using CSF-AI and multimodal MRI. Five Caucasian MPS IIIB patients (4 males, 1 female) with classic severe phenotype between 6 and 8 years of age were enrolled. Their mean age at the time of diagnosis of MPS IIIB was 2.4 years. A blood sample and CSF sample (by lumbar puncture) were obtained for determination of CSF-AI. DCE-MRI (Dynamic Contrast Enhanced-MRI) images were obtained before, during, and after intravenous injection of gadoterate meglumine (Dotarem®) contrast agent for determination of blood plasma volume, BBB transfer coefficient (Ktrans, reflecting BBB permeability) and the tissue MRI relaxation time, T1 (reflecting tissue physical properties). Exploratory biomarkers such as HS (in serum, urine, and CSF) and hepatocyte growth factor (HGF) levels in CSF were also evaluated in these patients. CSF-AI ranged between 5.5 to 11.3 in 4 out of 5 patients (upper limit of normal 4.9) with CSF-AI for the fifth patient below the upper limit of normal. DCE-MRI results showed Ktrans values in grey and white matter that were very low and similar to those previously reported in adult healthy brain, and T1 values in white matter that were comparable to normal volunteers of similar age. Other key findings from the MRI included cerebral atrophy, increased skull thickness and abnormal areas of white matter hyperintensity (Fig. 1). Exploratory biomarkers showed substantial increase in HS levels in CSF, serum and urine, and an increase in HGF in CSF (compared to normal range). In MPS IIIB patients, there is evidence of mild BBB leakage based on the CSF-AI findings; these findings are reflected in the absence of clear evidence for BBB leakage on MRI. MRI volumetric measurements were robust and showed global and tissue-specific atrophy in these patients. Thesefindingsmay have implications forMPS IIIB disease pathogenesis.

Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities.

The amyloid imaging agent, Pittsburgh Compound-B, binds with high affinity to β-amyloid (Aβ) in the brain, and it is well established that PiB also shows non-specific retention in white matter (WM). However, little is known about retention of PiB in areas of white matter hyperintensities (WMH), abnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to both cognitive dysfunction and Aβ deposition. The goal of the present study was to explore PiB retention in both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all subjects, regardless of WMH burden or size. (2) Subject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of subjects with high WMH compared to subjects with low WMH. Additionally, in subjects with high WMH, there was significantly lower PiB retention in subject-specific maps of WMH compared to NAWM, which was not observed in subjects with low WMH, likely because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights about the molecular basis of the non-specific retention of amyloid tracers in white matter.

Dystonie paroxystique et sclérose en plaques

IntroductionMovement disorders are uncommon in multiple sclerosis, except for tremor. Patients rarely have paroxysmal dystonia (or tonic spasm), which can be the presenting manifestation of the disease. ObservationsTwo videotaped observations are presented. The first patient was a 27-year-old woman, treated for relapsing-remitting multiple sclerosis, who presented daily several short (<1minute) paroxysms of right hemibody dystonia. Brain MRI revealed several areas of cerebral demyelination, including the posterior limb of the left internal capsule with gadolinium enhancement. These events disappeared 7 days after corticosteroid infusion. The second patient was a 62-year-old man who presented brief episodes (<1minute) of daily painful left hemibody dystonia. Three months later, similar paroxysms affecting the right hemibody including the face occurred. At times, the two hemibodies were affected simultaneously. The brain MRI showed multiple areas of white matter hyperintensity, including two symmetrical areas in the posterior limb of the internal capsules. Multiple sclerosis was diagnosed on clinical, MRI and biological data. Four days after starting corticosteroids, these paroxysmal phenomena disappeared totally. ConclusionDystonia is an under-recognized aspect of paroxysmal events during multiple sclerosis. It might involve ephaptic transmission among abnormal demyelinated neurons; this ectopic excitation can arise at variable levels of the corticospinal tract, but the analysis of reported cases and those described in this study shows that impairment of the posterior limb of the internal capsule seems to be a prevalent topography. Inflammation is likely to play a role because steroids often improve these phenomena. In this article, we review the clinical aspects, pathophysiology and outcome of paroxysmal dystonia in multiple sclerosis.

Atlas-derived perfusion correlates of white matter hyperintensities in patients with reduced cardiac output

Reduced cardiac output is associated with increased white matter hyperintensities (WMH) and executive dysfunction in older adults, which may be secondary to relations between systemic and cerebral perfusion. This study preliminarily describes the regional distribution of cerebral WMH in the context of a normal cerebral perfusion atlas and aims to determine if these variables are associated with reduced cardiac output. Thirty-two participants (72 ± 8 years old, 38% female) with cardiovascular risk factors or disease underwent structural MRI acquisition at 1.5T using a standard imaging protocol that included FLAIR sequences. WMH distribution was examined in common anatomical space using voxel-based morphometry and as a function of normal cerebral perfusion patterns by overlaying a single photon emission computed tomography (SPECT) atlas. Doppler echocardiogram data was used to dichotomize the participants on the basis of low (n=9) and normal (n=23) cardiac output. Global WMH count and volume did not differ between the low and normal cardiac output groups; however, atlas-derived SPECT perfusion values in regions of hyperintensities were reduced in the low versus normal cardiac output group (p<0.001). Our preliminary data suggest that participants with low cardiac output have WMH in regions of relatively reduced perfusion, while normal cardiac output participants have WMH in regions with relatively higher regional perfusion. This spatial perfusion distribution difference for areas of WMH may occur in the context of reduced systemic perfusion, which subsequently impacts cerebral perfusion and contributes to subclinical or clinical microvascular damage.

Non-arteritic anterior ischaemic optic neuropathy: evaluation of the brain and optic pathway by conventional MRI and magnetisation transfer imaging

The purpose of the study was to examine the brain and the visual pathway of patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using conventional MRI (cMRI) and volumetric magnetisation transfer imaging (MTI). Thirty NAION patients, aged 67.5 +/- 8.14 years, and 28 age- and gender-matched controls were studied. MTI was used to measure the magnetisation transfer ratio (MTR) of the chiasm and for MTR histograms of the brain. The presence of areas of white matter hyperintensity (WMH) was evaluated on fluid-attenuated inversion recovery (FLAIR) images. Area of the optic nerves (ONs) and volume of the chiasm were assessed, as were coronal short-tau inversion recovery (STIR) and MTI images, respectively. More areas of WMH were observed in patients (total 419; mean 14.4; SD 19) than in controls (total 127; mean 4.7; SD 5.7), P < 0.001. Area (in square millimetres) of the affected ONs, volume(in cubic millimetres) and MTR (in percent) of the chiasm (10.7 +/- 4.6), (75.8 +/- 20.2), (56.4 +/- 6.5), respectively, were lower in patients than in controls (13.6 +/- 4.3), (158.2 +/- 75.3) (62.1 +/- 6.2), respectively, P < 0.05. Mean MTR of brain histograms was lower in patients (53.0 +/- 8.0) than in controls (58.0 +/- 5.6), P < 0.05. NAION is characterised by decreased ON and chiasmatic size. The low MTR of the chiasm and brain associated with increased areas of WMH may be suggestive of demyelination and axonal damage due to generalised cerebral vascular disease.

Clinical and Neuroradiologic Features Associated With Chronicity in Late-Life Depression

The authors conducted a 6-year follow-up of 16 patients with late-life depression to evaluate the relationships between clinical and neuroradiologic variables and disease outcome. Patients had a comprehensive neuropsychiatric evaluation and magnetic resonance imaging (MRI) at baseline and follow-up. Eight of the 16 developed a chronic course of unremitting major depression sufficient to cause significant psychosocial impairment. Six patients with a chronic course and four patients with a non-chronic course of depression had white matter hyperintensities (WMH) on MRI at baseline. Four patients whose WMH increased in size over time developed a chronic unremitting course of depression. No patients with non-chronic depression had large areas of WMH at baseline or exhibited increased WMH size over time. Chronic depression was associated with severity of cerebrovascular risk factors, apathy, and poor quality of life. Treatment and prevention of cerebrovascular disease may improve the outcome of late-life depression.

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging.

To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.

Clinical and Neuroradiologic Features Associated With Chronicity in Late-Life Depression

The authors conducted a 6-year follow-up of 16 patients with late-life depression to evaluate the relationships between clinical and neuroradiologic variables and disease outcome. Patients had a comprehensive neuropsychiatric evaluation and magnetic resonance imaging (MRI) at baseline and follow-up. Eight of the 16 developed a chronic course of unremitting major depression sufficient to cause significant psychosocial impairment. Six patients with a chronic course and four patients with a non-chronic course of depression had white matter hyperintensities (WMH) on MRI at baseline. Four patients whose WMH increased in size over time developed a chronic unremitting course of depression. No patients with non-chronic depression had large areas of WMH at baseline or exhibited increased WMH size over time. Chronic depression was associated with severity of cerebrovascular risk factors, apathy, and poor quality of life. Treatment and prevention of cerebrovascular disease may improve the outcome of late-life depression. The authors conducted a 6-year follow-up of 16 patients with late-life depression to evaluate the relationships between clinical and neuroradiologic variables and disease outcome. Patients had a comprehensive neuropsychiatric evaluation and magnetic resonance imaging (MRI) at baseline and follow-up. Eight of the 16 developed a chronic course of unremitting major depression sufficient to cause significant psychosocial impairment. Six patients with a chronic course and four patients with a non-chronic course of depression had white matter hyperintensities (WMH) on MRI at baseline. Four patients whose WMH increased in size over time developed a chronic unremitting course of depression. No patients with non-chronic depression had large areas of WMH at baseline or exhibited increased WMH size over time. Chronic depression was associated with severity of cerebrovascular risk factors, apathy, and poor quality of life. Treatment and prevention of cerebrovascular disease may improve the outcome of late-life depression.

Cognition and white matter hyperintensities in older depressed patients.

The authors compared amounts of white matter hyperintensity in late- and early-onset depressed patients and never-depressed older subjects, compared neuropsychological function in these groups, and investigated the association between white matter hyperintensities and cognitive function in depression. Sixty currently depressed patients whose first depression occurred after age 50 years, 35 depressed patients over age 50 whose first depression occurred before age 35, and 165 nonpsychiatrically ill subjects over age 50 underwent magnetic resonance imaging (MRI) and neuropsychological evaluation. Areas of white matter hyperintensity were measured from MRI images. The late-onset patients had more white matter hyperintensity than either of the other groups. Compared to the nondepressed subjects, the patients had significantly lower scores in the cognitive domains of nonverbal intelligence, nonverbal memory, constructional ability, executive ability, and information processing speed. The cognitive abnormalities were mostly confined to the late-onset patients, and the presence of a large amount of white matter hyperintensity was associated with significantly poorer executive skills. However, most of the scores were not in the significantly impaired range. Large amounts of white matter hyperintensity are more frequent in patients with late-onsetdepression than in elderly subjects with early-onset or no depression. Both late- and early-onset elderly depressed patients show mild decrements in some "right hemisphere" cognitive skills; the late-onset subjects also show deterioration in information processing speed and executive functions. Patients with large amounts of white matter hyperintensity have significantly poorer executive function.