Magnetic resonance imaging cerebral abnormalities and neuropsychologic test performance in elderly hypertensive subjects. A case-control study.

OBJECTIVE: To search for a morphologic basis of cognitive impairment possibly associated with arterial hypertension using magnetic resonance imaging and a demanding neuropsychologic test battery. DESIGN: Case-control comparison with age, length of education, presence of diabetes, and presence of cardiac disease as matching criteria. SETTING: Austrian Stroke Prevention Study. SUBJECTS: A total of 89 hypertensive subjects and 89 control subjects from a subset of 272 volunteers with no neurologic symptoms undergoing extensive diagnostic workup in a large-scale stroke prevention study among randomly selected elderly community members. MAIN OUTCOME MEASURES: Focal brain abnormalities and size of ventricles and cortical sulci as assessed by magnetic resonance imaging and neuropsychological test scores. RESULTS: Hypertensive subjects more commonly showed areas of white matter hyperintensity and moderately severe ventricular enlargement compared with controls. While no differences were noted between the investigational groups in test results of memory capacity and conceptualization, hypertensive subjects tended to perform worse when assessed for attentional and visuopractical skills. These differences became significant when comparing the brain-damaged subsets of patients and controls with their counterparts without cerebral changes. The pattern and extent of neuropsychologic deficits was similar in hypertensive and normotensive subjects with abnormal magnetic resonance imaging scans. CONCLUSION: Our data strongly suggest the high rate of brain abnormalities among hypertensive subjects as the cause of their subtle neuropsychological dysfunction.

Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals.

To search for a morphologic basis of cognitive impairment possibly associated with essential hypertension, we studied 35 otherwise asymptomatic hypertensive individuals (mean age, 38.7 years; range, 22 to 49 years) and 20 normotensive control subjects (mean age, 37.9 years; range, 26 to 49 years) using neuropsychologic tests and magnetic resonance imaging. Irrespective of drug treatment, hypertensive individuals performed significantly worse than did control subjects when assessed for verbal memory and total learning and memory capacity, while there were no differences in test results of visual memory, attention, vigilance, and reaction time. The hypertensive individuals also described themselves as less active but ranked similar on five other mood subscales. Punctate high-signal intensities of the white matter were found almost twice as often in the hypertensive group (38%) as in the control group (20%). There was no difference in test performance between hypertensive individuals with and those without white matter lesions, however. Our results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.

Magnetic resonance imaging signal hyperintensities in the deep and subcortical white matter. A comparative study between stroke patients and normal volunteers.

Mixed population studies suggest a relationship between deep and subcortical white matter hyperintensities on magnetic resonance imaging and cerebrovascular disease. To further clarify this issue we compared the prevalence and extent of such signal abnormalities between a group of 133 consecutive stroke patients (mean age, 54.7 +/- 16.7 years) and 101 normal volunteers (mean age, 54.7 +/- 13.1 years). Diabetes and cardiac disease were significantly more common in patients than in normal subjects. Prevalence rates of clinically silent lesions were 44% and 47.5%, respectively. Beginning confluent and confluent foci were seen in 19.5% of patients, but in only 7.5% of normal subjects. Significant univariate correlations were found for the presence and extent of lesions with age, diabetes, cardiac disease, severity of extracranial carotid arteriosclerosis, and arterial hypertension, but not with the diagnosis of stroke or the type of brain infarction. Multivariate regression analysis established age and diabetes mellitus as the only independent predictors of white matter damage. We conclude that more extensive white matter abnormalities in stroke patients stem from their higher rate of cerebrovascular risk factors but are unrelated to the occurrence of ischemic attacks per se.

Assessment of MRI criteria for a diagnosis of MS.

To test the reliability of four previously proposed MRI criteria for the diagnosis of MS, we reviewed 1,500 consecutive brain scans for the presence, number, size, and location of areas of increased signal (AIS) on proton-density and T2-weighted images, unaware of the patients' clinical presentations and ages. This series included 134 subjects with a clinical diagnosis of MS. Relying exclusively on the presence of at least three or four AIS for a positive diagnosis of MS resulted in high sensitivity (90% for three AIS and 87% for four) but inadequate specificity (71% for three AIS and 74% for four) and positive predictive value (23% for three AIS and 25% for four). If one of these lesions was required to border the lateral ventricles, specificity was 92% and positive predictive value was 50% at a sensitivity of 87%. Using the Fazekas criteria (at least three AIS and two of the following features: abutting body of lateral ventricles, infratentorial lesion location, and size > 5 mm) led to a further highly significant improvement of specificity (96%; p = 0.0000) and increase of the positive predictive value (65%) at the expense of a less significant decrease in sensitivity (81%; p < 0.01).

Pathologic correlates of incidental MRI white matter signal hyperintensities.

We related the histopathologic changes associated with incidental white matter signal hyperintensities on MRIs from 11 elderly patients (age range, 52 to 82 years) to a descriptive classification for such abnormalities. Punctate, early confluent, and confluent white matter hyperintensities corresponded to increasing severity of ischemic tissue damage, ranging from mild perivascular alterations to large areas with variable loss of fibers, multiple small cavitations, and marked arteriolosclerosis. Microcystic infarcts and patchy rarefaction of myelin were also characteristic for irregular periventricular high signal intensity. Hyperintense periventricular caps and a smooth halo, however, were of nonischemic origin and constituted areas of demyelination associated with subependymal gliosis and discontinuity of the ependymal lining. Based on these findings, our classification appears to reflect both the different etiologies and severities of incidental MRI signal abnormalities, if it is modified to treat irregular periventricular and confluent deep white matter hyperintensities together.

Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis.

We reviewed the MRIs of 49 asymptomatic volunteers (age range, 31 to 77 years) and of 50 MS patients (age range, 14 to 63) for areas of increased signal (AIS) and features discriminating MS lesions from lesions seen with normal aging. We obtained optimal specificity of MRI interpretation (100%) if we required at least two of the following three AIS features--size greater than or equal to 6 mm, abutting ventricular bodies, infratentorial location--for a positive MRI diagnosis of MS. Applying these criteria to the MRIs of elderly patients with suspected MS should significantly improve specificity (p less than 0.001) over current quantitative criteria (at least three AIS greater than or equal to 3 mm) without significantly decreasing sensitivity.

Superficial siderosis of the spinal cord: a rare cause of myelopathy diagnosed by MRI.

Repeated bleeding into CSF spaces may cause superficial siderosis with progressive neurologic impairment. The unique physical properties of MRI provide a basis for the in vivo diagnosis of this entity.

Brain magnetic resonance imaging in coronary artery bypass grafts: a pre- and postoperative assessment.

We undertook a study to determine (1) the frequency and prognostic significance of preexisting MRI brain abnormalities in patients undergoing coronary artery bypass grafts (CABG) and (2) whether MRI can detect surgery-related brain damage in 31 neurologically asymptomatic CABG patients (mean age, 61.0 +/- 6.6 years). MRIs were performed within 7 days before and 8 to 17 days after surgery. When we compared the preoperative images with those of 31 age- and risk factor-matched neurologically asymptomatic controls free of cardiac disease (mean age, 60.3 +/- 6.1 years), higher rates of thromboembolic infarcts (16% versus 0%), lacunes (58.1% versus 32.3%), and brainstem lesions (22.6% versus 3.8%) were noted. Subjective rating demonstrated significantly larger ventricles in patients than in controls (p = 0.002). CABG candidates also had significantly increased ventricular-to-intracranial cavity ratios (VICR) as determined by semiquantitative volumetric measurements (6.9 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.0004). Eleven patients had postsurgical complications, with eight having symptoms consistent with diffuse encephalopathy. The only MRI finding that separated encephalopathic from complication-free patients was ventricular size (VICR 9.0 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.006). This difference remained statistically significant after adjustment for the effects of age (p = 0.04). Postoperative MRI consistently failed to demonstrate surgery-related brain damage responsible for the encephalopathy.

Neuropsychologic correlates of MRI white matter hyperintensities: a study of 150 normal volunteers.

To determine the effects of MRI white matter hyperintensities (WMH) on cognitive functioning, we used neuropsychologic tests and MRI to study 150 elderly volunteers free of neuropsychiatric or general disease. There were 76 (50.3%) individuals without and 74 (49.7%) with WMH. The latter subset was older (61.3 +/- 6.6 years versus 58.5 +/- 5.8 years, p = 0.005), had a higher mean arterial blood pressure (103.7 +/- 11.4 mm Hg versus 99.9 +/- 10.3 mm Hg, p = 0.03), and a larger ventricular-to-intracranial-cavity ratio (6.3 +/- 5.6% versus 4.7 +/- 1.6%, p = 0.02). Individuals with WMH performed worse than their counterparts without such abnormalities on all tests administered. After adjusting for the group differences in age, arterial blood pressure, and ventricular size, we noted statistically significant results on form B of the Trail Making Test (121.8 +/- 37.8 msec versus 100.3 +/- 47.9 msec, p = 0.04), a complex reaction time task (680.8 +/- 104.9 msec versus 607.1 +/- 93.9 msec, p = 0.001), and the assembly procedure of the Purdue Peg-board Test (27.5 +/- 5.8 versus 30.6 +/- 5.9, p = 0.02). Partial correlations did not reveal any relationship between test scores and the semiautomatically assessed total area of WMH. Our data suggest that the presence of WMH exerts a subtle effect on neuropsychologic performance of normal elderly individuals, which becomes particularly evident on tasks measuring the speed of more complex mental processing.

Estrogen replacement therapy in older women: a neuropsychological and brain MRI study.

OBJECTIVE: To determine if postmenopausal women receiving estrogen perform better on demanding cognitive tests than women without estrogen replacement and if this beneficial effect on cognition is caused by estrogen-related prevention of silent ischemic brain damage. DESIGN: Cross-sectional study comparing postmenopausal estrogen users and non-users. SETTING: Austrian Stroke Prevention Study. PARTICIPANTS: A total of 70 women currently using estrogen and 140 women who have never used estrogen from a subset of 222 postmenopausal women without neuropsychiatric or general disease undergoing extensive diagnostic work-up in a large-scale stroke prevention study among randomly selected community members. MEASUREMENTS: Neuropsychological test scores and focal brain abnormalities as well as size of ventricles and cortical sulci as assessed by 1.5 Tesla MRI. RESULTS: Estrogen users performed better than non-users on almost all neuropsychological tests administered. When ANCOVA was used to correct for slight differences between groups in age, length of education, mean arterial blood pressure and self-reported activation, values of P < .05 were noted on tasks assessing conceptualization, attention, and visuopractical skills. After adjustment for multiple comparisons, the differences in conceptualization and visuopractical skills remained significant. MRI showed a lower rate and extent of white matter hyperintensities and a significantly smaller total white matter hyperintensity area in women treated with estrogen (P = .043). The total white matter hyperintensity area was inversely related to the duration of estrogen replacement therapy(P = .040). However, there was no difference in neuropsychological performance between estrogen users with and without white matter abnormalities, and this was also supported by the lack of an association between cognitive test results and the extent of white matter disease. CONCLUSIONS: Our study demonstrated an association between estrogen replacement therapy and better cognitive functioning and a lower rate of clinically unsuspected ischemic brain damage in postmenopausal women.

MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

The morphologic correlate of incidental punctate white matter hyperintensities on MR images.

Postmortem examinations were made of the brains of six patients, 52-63 years old, who exhibited incidental punctate white matter hyperintensities on MR images before death. Our aim was to unravel the morphologic correlate of such lesions. By repeating the MR study after fixation on four specimens, cutting the brain parallel to the MR imaging plane, and examining whole-hemisphere microscopic sections, we optimized lesion identification. The white matter signal abnormalities were better delineated on pre- than postmortem scans, and visual inspection of the brain slices was normal in all but one location. Histologically, we found areas of reduced myelination with atrophy of the neuropil around fibrohyalinotic arteries as well as different stages of perivenous damage. The latter ranged from spongiform transformation of the neuropil and scattered foci of demyelination to large perivenous areas with marked rarefaction of myelinated fibers. Edematous glial swelling in foci of ganglion cell heterotopia caused subcortical white matter hyperintensities in one case. Our results suggest minor perivascular damage but not infarction as the most likely substrate of punctate MR white matter hyperintensities in elderly brains. Histologic correlations with MR images obtained during life or with studies of unfixed material are necessary to analyze such small lesions.

MR of cerebral abnormalities concomitant with primary intracerebral hematomas.

PURPOSE: To determine whether arteriolar vessel wall degeneration in primary intracerebral hematomas might be associated with ischemic brain lesions and clinically silent (apparently intracerebral) previous hemorrhages. METHODS: The MR images of 120 consecutive patients (mean age, 60 years; age range, 22 to 84 years) with their first stroke caused by a primary intracerebral hematoma were reviewed retrospectively for coexisting ischemic damage and previous bleeds. RESULTS: Early confluent to confluent white matter hyperintensities, lacunes, or infarction were present in 83 (69%) of the patients, and 39 (33%) had had previous hemorrhages consisting of microbleeds or old hematomas. Extensive white matter hyperintensities and lacunes were most frequent in patients with thalamic primary intracerebral hematomas. There was no relationship between the frequency of old hemorrhages and the location of subsequent primary intracerebral hematomas. CONCLUSION: Clinically silent ischemic lesions and previous hemorrhages are a common finding on MR images of patients with primary intracerebral hematoma. They may therefore serve as evidence of diffuse microangiopathy with a possible increased risk for cerebral hemorrhage.

Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment.

Although both morphologic cerebral damage and cognitive dysfunction are known to occur in patients on chronic hemodialysis (CHD) their extent and possible relation have been rarely studied. We therefore performed magnetic resonance imaging of the brain and neuropsychological testing in 30 consecutive CHD patients (mean age 58 years; range 37-69) and in an equal number of asymptomatic volunteers matched for age, sex and major cerebrovascular risk factors. Twenty-four (80%) of the CHD patients were demented according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IIIR and their mean scores on the Mini Mental State Examination (22.9 +/- 4 vs. 27.9 +/- 1.4; p < 0.001) and Mattis Dementia Rating Scale (112.3 +/- 21.5 vs. 141.9 +/- 2.3); p < 0.001) were significantly lower than those of controls. The brains of CHD patients showed significantly more atrophy on visual rating and semiquantitative morphometric measures. Multiple lacunes or confluent white matter hyperintensities predominated in 10 (33%) patients, three showed territorial infarcts and two a combination of both. Clinically these findings were unexpected in almost half of individuals. Marked cognitive impairment was associated with more extensive enlargement of the third ventricle (5.8 +/- 1.8 vs. 7.3 +/- 2 mm; p < 0.04) and the temporal horns (3.5 +/- 1.6 vs. 5.1 +/- 1.8 mm; p < 0.02) but not with the presence of cerebral ischemic lesions or any difference in laboratory data. These results call attention to a very high rate of cerebral damage in individuals undergoing CHD and suggest brain degeneration of probably toxic-metabolic etiology to be associated with severe cognitive impairment of these patients.

The relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease.

To further elucidate the relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease (AD) we performed a case-control comparison between 30 consecutive patients with probable AD (age range 49-76, mean 65 years) and 60 asymptomatic volunteers matched for age, sex, and major cerebrovascular risk factors. We used a 1.5T magnet and determined the extent of morphologic abnormalities both by visual grading and measurement. AD patients showed comparable grades of deep/subcortical white matter hyperintensities (WMH) and a similar extent of the total WMH area as controls (3.3 cm2 +/- 8.8 vs. 2.0 cm2 +/- 4.6). They had significantly more often a "halo' of periventricular hyperintensity (PVH) (p < 0.0005) and an increased mean PVH thickness (3.0 mm +/- 1.9 vs. 1.3 mm +/- 1.2; p < 0.001). This PVH thickness correlated significantly with measures of ventricular enlargement. While univariate logistic regression also suggested a significant association of PVH thickness with a diagnosis of AD this association was lost against atrophy measures in a multivariate analysis. Our results confirm a significantly greater extent of PVH in AD patients than controls even when matched for cerebrovascular risk factors. However, this abnormality was not independently related to the disease but rather appears to be an epiphenomenon of brain atrophy.

Magnetic resonance imaging and spectroscopy of progressive cerebral involvement in Kearns Sayre Syndrome.

Kearns Sayre Syndrome (KSS) belongs to the group of so called 'mitochondrial encephalopathies'. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) may have the potential to noninvasively detect and monitor disease specific cerebral involvement, as we wish to demonstrate in a patient whom we have followed for 3.5 years. At first presentation with incomplete external ophthalmoplegia, ptosis, pigmentary retinopathy and impaired hearing MRI demonstrated ill defined areas of symmetric T2-prolongation in the dorsal parts of the mesencephalon, the pons and in both cerebellar hemispheres. While the patients clinical symptoms deteriorated, including the onset of dysphagia, signal abnormalities spread downwards into the medulla oblongata involving the glossopharyngeal nuclei and supratentorially into the white matter. Proton MRS performed with the PRESS sequence (TR/TE 1500/136 ms) in the area of white matter damage showed a doublet at 1.33 ppm, which is characteristic for the presence of lactate. Our findings suggest MRI abnormalities to increase in parallel with neurologic progression of KSS and confirm the utility of 1H-MRS in supporting mitochondrial respiratory chain insufficiency as the underlying cause of parenchymal alterations.

Risk factors for microangiopathy-related cerebral damage in the Austrian stroke prevention study.

Microangiopathy-related cerebral damage (MARCD) represents a common incidental MRI observation in the elderly. The risk factors of such findings are widely unknown. We therefore performed MRI in 349 randomly selected volunteers (ages 50 to 70 years) without neuropsychiatric disease, and evaluated the association of MARCD with conventional and recently suggested cerebrovascular risk factors such as apolipoprotein E genotypes, plasma concentrations of essential antioxidants and anticardiolipin antibody titres. MARCD was defined as evidence of early confluent and confluent deep white matter hyperintensities and lacunes. It was present in 71 (20.3%) subjects. Individuals with MARCD were older than those without such findings (62.7 years vs 59.6 years; P=0.0001). They had a higher rate of arterial hypertension (45.1% vs 28.1%; P=0.006) and cardiac disease (50.7% vs 37.1%; P=0.04), higher systolic blood pressure readings at exam (144.4 mmHg vs 136.7 mmHg; P=0.004), and higher serum fibrinogen concentrations (327.1 mg/dl vs 292.5 mg/dl; P=0.001). Their levels of total cholesterol (217.6 mg/dl vs 231.2; P=0.009), apolipoprotein A-I (167.3 mg/dl vs 177.4 mg/dl, P=0.02), lycopene (0.17 micromol/l vs 0.24 micromol/l; P=0.003), retinol (1.91 micromol/l vs 2.10 micromol/l; P=0.02) and alpha-tocopherol (27.55 micromol/l vs 31.14 micromol/l; P=0.001) were significantly lower. Forward stepwise regression analysis created a model of independent predictors of MARCD with age entering first (odds ratio 2.01/10 years), fibrinogen second (odds ratio 2.45/100 mg/dl), alpha-tocopherol third (odds ratio 0.55/10 micromol/l), and arterial hypertension fourth (odds ratio 1.96). The association of MARCD with various treatable clinical conditions may have preventive implications.

The diagnostic impact of magnetic resonance imaging on the evaluation of suspected spinal cord disease.

The data from 262 patients studied consecutively for suspected spinal cord disease were analysed to determine the utility of magnetic resonance imaging (MRI) in this clinical setting. Damage to the spinal cord was detected in a total of 188 (72%) patients and was caused by myelocompression in two thirds and by intramedullary lesions in one third of the patients. Misleading sensory levels 5 to 12 segments below the actual lesion site were seen in 26% of patients with both extra- and intramedullary types of abnormality. A negative spinal MRI implied predominantly demyelinating or inflammatory origin of the clinical symptomatology, as was indicated by additional MRI studies of the brain and CSF findings. It is concluded that MRI is the procedure of choice for assessing patients with medullary symptoms. Irrespective of localizing neurologic findings the evaluation of the entire spine and even of the brain may be necessary to obtain maximum diagnostic information.

Magnetic resonance imaging correlates of transient cerebral ischemic attacks.

BACKGROUND AND PURPOSE: MRI of patients with a transient ischemic attack (TIA) may provide more detailed morphological insights than CT. We therefore studied the frequency and type of TIA-related infarcts shown by MRI, examined the utility of intravenous contrast material, and searched for potential predictors of infarct occurrence. METHODS: We performed 1.5-T MRI of the brain of 52 patients (age range, 28 to 93 years; mean, 61 years) with a hemispheric TIA. Contrast material (Gd-DTPA) was given to 45 individuals. We recorded type, number, size, and location of ischemic brain lesions and related the presence of acute infarction to features of clinical presentation and probable causes for the TIA. RESULTS: MRI showed focal ischemic lesions in 50 patients (81%), but an acute TIA-associated infarct was seen in only 19 subjects (31%). In patients with an acute lesion, the infarcts were smaller than 1.5 cm in 13 (68%), purely cortical in 11 (58%), and multiple in 7 (37%) individuals. Contrast enhancement contributed to the delineation of an acute lesion in only 2 of 45 patients (4%). Acute infarction was unpredictable by clinical TIA features, but the frequency of identifiable vascular or cardiac causes was significantly higher in those patients with TIA-related morphological damage (odds ratio, 5.2 [95% confidence interval, 1.6 to 17.3]). CONCLUSIONS: More than two thirds of TIA patients showed no associated brain lesion even when MRI and contrast material were used, but the overall frequency of ischemic damage was high. TIA-related infarcts on MRI were mostly small and limited to the cortex and tended to consist of multiple lesions. A positive MRI underscores the need for comprehensive diagnostic workup since evidence of infarction appears to be associated with a higher frequency of significant vascular or cardiac disorders.