Hans Offenbacher

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.

White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors.

We studied 52 asymptomatic subjects using magnetic resonance imaging, and we compared age-matched groups (51-70 years old) with and without white matter lesions with respect to carotid ultrasonography, cerebral blood flow (xenon-133 injection), and cerebrovascular risk factors. In the group with white matter signal abnormalities, we noted a higher frequency of extracranial carotid artery disease, a lower mean gray matter blood flow (F1), and a significant reduction (p less than 0.05) in blood flow of the slow-flowing (F2) compartment. Hypertension, diabetes mellitus, and cardiac diseases (p less than 0.002) were found more often in this group. Our results indicate that a higher incidence of changes known to be associated with an increased risk for stroke exists in the presence of white matter lesions in normal elderly individuals.

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 ≥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 < 0.001) over current quantitative criteria (at least three AIS≥3 mm) without significantly decreasing sensitivity.

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 = 0.0051, 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 Pegboard 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.

Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals.

The incidence, average number, and localization of lesions of the white matter detected by the T2-weighted nuclear magnetic resonance images among volunteers without cerebrovascular symptoms have been correlated with the number of risk factors for stroke. Accepted risk factors were arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia, and cardiac disease. The 42 subjects examined were divided into Group A (0-1 risk factor, mean age 59.36 +/- 5.73 years), Group B (2 risk factors, mean age 61.54 +/- 8.33 years), and Group C (greater than or equal to 3 risk factors, mean age 62.57 +/- 9.83 years). Multiple risk factors among the age-matched groups was accompanied by a highly significant increase (p less than 0.001, Group A versus Group B; p less than 0.01, Group A versus Group C) of the incidence of white matter lesions. The average number of white matter lesions was increased (p less than 0.001) when Group A was compared with Groups B and C. Ninety-two percent of the white matter lesions were localized in watershed zones. Only 11 of the 155 abnormalities of the white matter detected by nuclear magnetic resonance imaging could be detected by computed tomography. White matter lesions in T2-weighted images appear to be an early stage of cerebrovascular disease.

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 prevalence of cerebral damage varies with migraine type : a MRI study

SYNOPSIS

Phenotypes of the N88S Berardinelli–Seip congenital lipodystrophy 2 mutation

Recently, two missense mutations (N88S, S90L) in the Berardinelli–Seip congenital lipodystrophy gene have been identified in autosomal dominant distal hereditary motor neuropathy and Silver syndrome. We report the phenotypic consequences of the N88S mutation in 90 patients of 1 large Austrian family and two unrelated German families. Variation in the clinical and electrophysiological phenotype enabled us to distinguish six subtypes. In 4.4%, the disorder was not penetrant. Twenty percent of the patients were subclinically affected; some of these patients could only be detected by pathological nerve conduction studies. A distal hereditary motor neuropathy type V phenotype characterized by predominant hand muscle involvement was found in 31.1%, whereas 14.5% showed typical Silver syndrome with amyotrophy of the small hand muscles and spasticity of the lower extremities. Moreover, the phenotype present in 20% was compatible with Charcot–Marie–Tooth disease. In 10%, the clinical diagnosis of pure or complicated hereditary spastic paraparesis was made. Electrophysiological studies showed an axonal neuropathy but also chronodispersion of compound motor action potentials and conduction blocks. Sensory nerve conduction studies were rarely pathological. Our study indicates that the dominant N88S mutation in the Berardinelli–Seip congenital lipodystrophy gene 2 leads to a broad spectrum of motor neuron disorders. Ann Neurol 2005;57:415–424

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.