Gudrun Roob

MRI evidence of past cerebral microbleeds in a healthy elderly population

Background: Incidental foci of signal loss suggestive of past microbleeds are a frequent finding on gradient-echo T2*-weighted MRI of patients with nontraumatic intracerebral hemorrhage and have been associated with bleeding-prone microangiopathy. If and to what extent such lesions may also occur in the normal population is unclear. Objective: To determine focal hypointensities in asymptomatic elderly individuals and their relation to other clinical and morphologic variables. Methods: T2*-weighted MRI of the brain was performed in a consecutive series of 280 participants (mean age 60 years, range 44 to 79) of the Austrian Stroke Prevention Study. This cohort consisted of randomly selected individuals without history or signs of neuropsychiatric disorder. Results: Past microbleeds ranging from one to five foci of signal loss were seen in 18 (6.4%) individuals. They were strongly associated with higher age, hypertension, and lacunes (p < 0.001), and extensive white matter damage was more frequently noted (p = 0.02). Hypertension was present in all individuals with focal hypointensities in the basal ganglia and infratentorially but in only 5 of 10 volunteers with microbleeds limited to cortico-subcortical sites (p = 0.04). Conclusions: MRI evidence of past microbleeds may be found even in neurologically normal elderly individuals and is related, but not restricted, to other indicators of small vessel disease. The predictive potential of this finding regarding the risk of intracerebral bleeding requires further investigation.

Frequency and Location of Microbleeds in Patients With Primary Intracerebral Hemorrhage

Background and Purpose MRI is known to detect clinically silent microbleeds (MBs) in patients with primary intracerebral hemorrhage (pICH), but the frequency and diagnostic and clinical significance of this finding are still debated. Therefore, we investigated a consecutive series of pICH patients and analyzed the patterns of MB distribution in the context of clinical variables and location of the symptomatic hematoma. Methods The study population consisted of 109 patients with pICH. There were 59 women and 50 men aged 22 to 91 years (mean 64.6 years). MRI was obtained on a 1.5-T system with use of a gradient-echo T2*-weighted sequence. A cohort of 280 community-dwelling asymptomatic elderly individuals who underwent the same imaging protocol served for comparison. Results MBs were seen in 59 (54%) patients and ranged in number from 1 to 90 lesions (mean 14, median 6). In the majority of patients, MBs were located simultaneously in various parts of the brain, with a preference for cortical-subcortical regions (39%) and the basal ganglia/thalami (38%). There was some tendency toward a regional association between MB location and the site of the symptomatic hematoma, but we could not discern specific patterns of MB distribution. Logistic regression analysis identified MBs, periventricular hyperintensity grades, and lacunes but not risk factors as independent variables contributing to a correct classification of pICH and control individuals. Conclusions MBs can be detected in more than half of the patients with pICH and appear to be quite general markers of various types of bleeding-prone microangiopathy.

The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates

Magnetic resonance imaging (MRI) has dramatically increased our ability to detect morphological abnormalities in relation to aging of the brain. Among those changes are alterations of the white matter which display high signal intensity on both proton density and T2-weighted images. They may be seen in the deep and subcortical white matter or in a periventricular location. In clinically asymptomatic individuals the reported prevalence ranges from 20% to 60% for deep and subcortical white matter hyperintensities and from 15% to 94% for periventricular changes. Besides different characteristics of the populations examined these wide ranges are a consequence of quite diverse rating schemes and measurement approaches. Inadequate grading of MRI hyperintensities may also explain some of the inconsistencies in the reported associations of white matter damage with cerebrovascular risk factors or cognitive functions. Therefore development of a commonly accepted rating scheme would be desirable. Histopathologic observations could lay the basis. Hyperintense periventricular capping of the frontal horns and a smooth halo of periventricular hyperintensity have been linked to disruption of the ependymal lining, subependymal gliosis and concomitant loss of myelin. Punctate lesions in the deep and subcortical white matter corresponded to minor perivascular reduction in myelin content possibly because of a lower permeability of thickened arteriolar walls. Larger patchy and confluent hyperintensities, however, appear to indicate more extensive ischemic damage consistent with advanced microangiopathy. In parallel, newer MRI techniques may also contribute to the delineation and separation of these various types of tissue alteration.

Plasma Antioxidants and Cognitive Performance in Middle‐Aged and Older Adults: Results of the Austrian Stroke Prevention Study

OBJECTIVES: To study the association between cognitive status and plasma concentrations of various antioxidants in middle‐aged and older individuals without neuropsychiatric disease.

Magnetic resonance imaging of cerebral microbleeds.

Magnetic resonance imaging of patients with primary intracerebral haemorrhage has drawn attention to focal areas of signal loss, which were suggested to indicate hemosiderin deposition from earlier bleeds. Correlative histopathologic data have recently confirmed this assumption and support a strong association between the occurrence of microbleeds and various types of small vessel disease, such as hypertensive lipofibrohyalinosis and cerebral amyloid angiopathy. Therefore, microbleeds that are detectable by magnetic resonance imaging could be viewed as markers for vessel wall disorders with a higher tendency for intracerebral bleeding. This finding appears to be of diagnostic importance, but could also help to predict a patients risk for spontaneous rebleeding or bleeding complications after anticoagulation.

Peripheral facial palsy: etiology, diagnosis and treatment.

Treatment options for peripheral facial palsy (PFP) are an often discussed problem in neurologic practice. Following a short description of the complex anatomy of the seventh cranial nerve we therefore review possible etiologies in the context of leading clinical signs, with idiopathic PFP or Bell’s palsy (BP) being most frequent. A rather typical clinical course of BP allows to focus differential diagnostic workup predominantly on the rapid identification of treatable infections such as with Herpes zoster or Borrelia burgdorferi. Neuroimaging studies are needed only in case of trauma, with slowly developing PFP or in the presence of associated signs and symptoms. As BP is characterized by an overall high rate of spontaneous recovery, major emphasis has to be put on avoiding complications by protecting the eye. Meta-analysis of four randomized controlled studies suggests a marginal benefit of steroids concerning eventual achievement of complete recovery. Beneficial effects of a combination of acyclovir and prednisone have also been claimed. While such therapies may be considered in patients with a presumptive bad prognosis, more general recommendations on medical treatment of BP will have to await further trials.

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.

Pyogenic Infectious Spondylitis: Clinical, Laboratory and MRI Features

Pyogenic infectious spondylitis (PIS) is an uncommon but serious inflammatory disorder of the discovertebral junction with frequent involvement of neural structures including the spinal cord. We report a series of 41 patients (age range 21-75 years, mean age 59 years) with primary PIS confirmed by signal abnormality of the intervertebral disk and adjacent vertebral bodies on magnetic resonance imaging. The prevailing clinical symptom was focal back pain aggravated by percussion in 90% of patients. Radicular signs or symptoms were present in 59% and spinal cord symptoms in 29% of patients, respectively. Evidence of inflammation consisted of an elevated sedimentation rate in 76%, leukocytosis in 61% and fever in 61% of individuals. Predisposing factors such as diabetes mellitus, previous nonspinal surgery and other sites of infection or inflammation were identified in 17 (41%) patients and 30 (73%) were older than 50 years. The lumbar spine was most often affected and PIS was associated with an epidural abscess in 15 (37%) patients. Increased alertness for PIS in the context of focal back pain with clinical or laboratory signs of inflammation is needed to speed up its detection.

MRI Cerebral White Matter Lesions and Paraoxonase PON1 Polymorphisms Three-Year Follow-Up of the Austrian Stroke Prevention Study

White matter lesions (WMLs) on magnetic resonance imaging (MRI) scans of older persons are thought to be caused by cerebral small-vessel disease. As they progress, these brain abnormalities frequently result in cognitive decline and gait disturbances, and their predictors are incompletely understood. Genetic risk factors have been implicated but remain undetermined so far. We examined whether 2 common polymorphisms of the paraoxonase (PON1) gene leading to a methionine (M allele)-leucine (L allele) interchange at position 54 and an arginine (B allele)-glutamine (A allele) interchange at position 191 are associated with the presence and progression of WMLs. We studied 264 community-dwelling subjects without neuropsychiatric disease (ages 44 to 75 years). All underwent vascular risk factor assessment, brain MRI, and PON1 genotyping. MRI scanning was repeated after 3 years. The extent and number of WMLs were recorded by 3 independent readers. Progression of WMLs was assessed by direct scan comparison. The final rating relied on the majority judgment of the 3 readers. The LL, LM, and MM genotypes were noted in 111 (42.0%), 118 (44.7%), and 35 (13.3%) subjects, respectively; the AA, AB, and BB genotypes occurred in 146 (55.3%), 98 (37.1%), and 20 (7.8%) individuals, respectively. Carriers of the LL genotype showed a nonsignificant trend toward more extensive WMLs and more frequently demonstrated lesion progression over the 3-year observation period (P=0.03). The polymorphism at position 191 had no effect. Logistic regression analysis yielded age (odds ratio, 1.08/y), diastolic blood pressure (odds ratio, 1.05/mm Hg), and LL paraoxonase genotype (odds ratio, 2. 65) to be significant predictors of WML progression. These data suggest that the LL PON1 genotype at position 54 influences the extent and progression of WMLs in elderly subjects.

Longitudinal change of white matter abnormalities

A three year follow-up of 273 participants (mean age 60+/-6.1 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity in elderly individuals without neuropsychiatric disease. Lesion progression was found in a total of 49 (17.9%) individuals. It was minor in 27 (9.9%) and marked in 22 (8.1%) participants. Diastolic blood pressure (odds ratio 1.07/mmHg) and early confluent or confluent white matter hyperintensities at baseline (odds ratio 2.62) were the only significant predictors of white matter hyperintensity progression. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period.