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Background and ObjectivesThere is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide.MethodsWe performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18–50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression.ResultsWe included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas “other determined stroke” and “undetermined stroke” were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42–4.36).DiscussionEthnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Stroke is currently the fifth highest cause of death in the United States and a leading cause of long-term disability.1 While physicians, patients, and their families crave answers regarding potential prognosis immediately after infarct, few tools currently exist for such predication, especially in the acute setting. For many years, the recovery literature focused on improvement in motor function. More recently, attention has shifted toward cognition, which can be substantially impaired after even minor stroke.2,3 This dysfunction can be progressive4 and may therefore affect long-term prognosis and reduce quality of life.2,3,5 Cognitive dysfunction, however, not only may be an important component of a poor long-term outcome but also may serve as a predictor for those at highest risk of functional decline after stroke.

We investigated longitudinal changes in iron concentration in the subcortical gray matter (caudate nucleus, globus pallidus, putamen, thalamus) of patients with clinically isolated syndrome (CIS) and definite multiple sclerosis (MS) and their relation to clinical and other morphologic variables.We followed 144 patients (76 CIS; median Expanded Disability Status Scale [EDSS] 1.0 [interquartile range (IQR) 0.0-2.0]; 68 MS; median EDSS 2.0 [IQR 1.0-3.3]) clinically and with 3T MRI over a median period of 2.9 (IQR 1.3-4.0) years. Iron concentration was determined by R2* relaxometry at baseline and last follow-up.At baseline, subcortical gray matter iron deposition was higher in MS compared to CIS. In CIS, R2* rates increased in the globus pallidus (p0.001), putamen (p0.001), and caudate nucleus (p0.001), whereas R2* rates in the thalamus decreased (p0.05). In MS, R2* rates increased in the putamen (p0.05), remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus (p0.01). Changes in R2* relaxation rates were unrelated to changes in the volume of respective structures, of T2 lesion load, and of disability.Iron accumulation in the basal ganglia is more pronounced in the early than later phases of the disease and occurs independent from other morphologic brain changes. Short-term changes in iron concentration are not associated with disease activity or changes in disability.

A 55-year-old otherwise healthy woman presented with sudden-onset anterograde amnesia, temporal disorientation, and repetitive questioning, which was associated with moderate intensity headache. Consistent with transient global amnesia (TGA), this clinical symptomatology lasted for 8 hours. Brain imaging showed a convexal subarachnoid hemorrhage1 (cSAH) (figure, A) and—characteristic of TGA2—a punctuate diffusion-weighted imaging positive lesion in the right hippocampus on MRI (figure, B and C). Cerebral microbleeds or cortical superficial siderosis were not evident on acute MRI.

Objective: To report about a possible association between fingolimod treatment and tumefactive demyelinating lesions (TDL) as seen in a patient developing repeated TDL on continued fingolimod therapy. Methods: We performed serial clinical and radiologic assessments and immunophenotyping of blood and CSF immune cells. We also present a literature review about recent similar cases. Results: Clinical course and radiologic findings were consistent with diagnosis of TDL. Immune cell phenotyping showed pronounced shifts in the immune cell composition related to fingolimod treatment. In addition, we observed a subset of highly differentiated effector cells (CD45R0negCCR7neg) within the CD8+ T-cell population, which was about 2-fold enriched in the CSF compared to the peripheral blood. Conclusion: Our observations add further evidence for the development of atypical demyelinating lesions in some patients receiving fingolimod. These might be related to a treatment-associated shift in the immunopathology of specifically susceptible individuals.

Atherosclerosis is believed to be a minor cause of TIA and stroke in younger and middle-aged patients. However, data from large cohorts are limited. This study investigates the prevalence of extracranial and intracranial atherosclerosis in stroke and TIA patients aged 18-55 years in the multinational sifap1 study.From the sifap1 cohort (n = 5,023), we analyzed a subset of patients with complete data from carotid ultrasound studies. Patients with arterial dissections, vasculitis, and mobile thrombi were excluded. Among the remaining 2,187 patients (men: n = 1,319; 18-44 years: n = 744), intracranial arteries were additionally examined with ultrasonography in 1,612 patients (73.7%). Patients were stratified by sex and age groups (younger: 18-44 years; middle-aged: 45-55 years).In patients with ischemic stroke, the overall prevalence of carotid artery stenoses and occlusions was 8.9% (younger: 4.9%; middle-aged: 11.0%), of which 81% were symptomatic. Nonstenotic carotid plaques were more common in men than in women (15.8% vs. 7.7%; p0.001), and in middle-aged than in younger patients (17.0% vs. 4.9%; p0.001). Supratentorial intracranial artery stenoses and occlusions amounted to 11.8%. Supratentorial stenoses occurred more frequently in middle-aged patients (13.0% vs. 7.8%; p0.001), whereas occlusions were equally common (both 3.2%; not significant).We observed a substantial proportion of atherosclerotic carotid artery stenoses and occlusions in younger stroke patients. Intracranial stenoses and occlusions were even more prevalent than extracranial carotid artery disease. Together with nonstenotic plaques, one-fifth of patients (21.2%) had symptomatic or asymptomatic large-artery atherosclerosis, which should encourage future stroke prevention campaigns to target risk factor modification in young people.

A 73-year-old woman presented with acute lower back pain and right sensory radicular L4 syndrome. Spinal MRI showed a cranially shifted T2-hypointense mass suspicious for disc herniation in the L3/4 segment with compression of the right nerve root L4 (figure 1). Due to atypical morphology, CT was performed and disclosed an intraspinal epidural gas bubble mimicking disc herniation on MRI (figure 2). In association with coexisting intravertebral vacuum disc phenomenon (figure 2B), it appears likely that the gas gained access to the epidural space after annulus fibrosus rupture.1 Vacuum disc phenomenon results from the accumulation of gas (mostly nitrogen) within the crevices of the disc as it degenerates.1

Objectives: Cognitive dysfunction (CD) is frequent in multiple sclerosis (MS) and can occur at early stages. Whereas functional reorganization with disease progression has been described for the motor system in MS using fMRI, no such studies exist for cognition. We attempted to assess the concept of functional reorganization concerning cognition using a simple “Go/No-go” fMRI paradigm. Methods: Patients with a clinically isolated syndrome (CIS, n = 10), relapsing-remitting MS (RRMS) (n = 10), or secondary progressive MS (SPMS) (n = 10), and 28 healthy controls (HC), underwent a comprehensive neuropsychological test battery, clinical examination, structural imaging, and an fMRI Go/No-go discrimination task at 3 T. Results: Patients performed worse than HC regarding memory, sustained attention and concentration, and information processing. These differences were driven by patients with SPMS. The fMRI task elicited activation in a widespread network including bilateral mesial and dorsolateral frontal, parietal, insular, basal ganglia, and cerebellar regions. Task performance was similar between phenotypes, but deviation from the activation pattern observed in HC and patients with CIS increased with disease progression. Patients with RRMS showed increased brain activation in the precuneus, both superior parietal lobes, and the right fusiform gyrus, and recruited the hippocampus with increasing demands. Patients with SPMS demonstrated the most abnormal network function, including recruitment of pre-SMA, bilateral superior and inferior parietal, dorsolateral prefrontal, right precentral, bilateral postcentral, and right temporal brain areas. Conclusion: Using a cognitive fMRI paradigm, we were able to confirm adaptive changes of neuronal activation with progressing MS and to provide strong evidence for their compensatory nature, at least partially.

Background: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. Objective: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. Methods: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. Results: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. Conclusions: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Cerebral amyloid angiopathy (CAA) leads to considerable morbidity and mortality through recurrent lobar intracerebral hemorrhages (ICH). In clinical practice, it is a challenge to identify patients at high risk for a recurrence because of limited clinical and neuroimaging predictors for rebleeding.

Objective: To determine whether chronic alcohol consumption or acute alcohol intoxication affects the rate of IV thrombolysis (IVT) and associated risk of symptomatic intracranial hemorrhage (SICH) in patients with acute ischemic stroke (IS). Methods: We analyzed data from the nationwide Austrian Stroke Unit Registry for all patients with IS admitted to one of 35 stroke units between 2004 and 2014. We compared demographic and clinical characteristics for patients with chronic alcohol consumption (>2 drinks/d) or acute intoxication and for patients without these factors and their rates of IVT and associated SICH. Results: We identified 47,422 patients with IS. Of these patients, 3,999 (8.5%) consumed alcohol chronically and 216 (0.5%) presented with acute intoxication. Alcohol abusers were younger, more frequently men, and less often functionally disabled before the index event. Stroke severity was comparable between alcoholic and nonalcoholic IS patients. Nevertheless, patients who abused alcohol were less likely to receive IVT (16.6% vs 18.9%) and this difference remained after accounting for possible confounders. Rates of SICH after IVT were not increased in patients who abused alcohol (2.1% vs 3.7%, p = 0.04). Multivariate analysis including age, NIH Stroke Scale score, and time from symptom onset to IVT treatment showed that alcohol abuse was not an independent risk factor for SICH and was not protective (odds ratio 0.73, 95% confidence interval 0.43–1.25, p = 0.2). Conclusions: IS patients with chronic alcohol consumption or acute intoxication have decreased likelihood of receiving IVT and are not at an increased risk of associated SICH. This supports current practice guidelines, which do not list chronic alcohol consumption or acute intoxication as an exclusion criterion.

Objectives: To determine the rate of brain atrophy in neurologically asymptomatic elderly and to investigate the impact of baseline variables including conventional cerebrovascular risk factors, APOE e4, and white matter hyperintensity (WMH) on its progression. Methods: We assessed the brain parenchymal fraction at baseline and subsequent annual brain volume changes over 6 years for 201 participants (F/M = 96/105; 59.8 ± 5.9 years) in the Austrian Stroke Prevention Study from 1.5-T MRI scans using SIENA (structural image evaluation using normalization of atrophy)/SIENAX (an adaptation of SIENA for cross-sectional measurement)(www.fmrib.ox.ac.uk/fsl). Hypertension, cardiac disease, diabetes mellitus, smoking, and regular alcohol intake were present in 64 (31.8%), 60 (29.9%), 5 (2.5%), 70 (39.3%), and 40 (20.7%) subjects, respectively. Plasma levels of fasting glucose (93.7 ± 18.6 mg/dL), glycated hemoglobin A (HbA 1c ; 5.6 ± 0.7%), total cholesterol (228.3 ± 40.3 mg/dL), and triglycerides (127.0 ± 75.2 mg/dL) were determined. WMH was rated as absent (n = 56), punctate (n = 120), early confluent (n = 14), and confluent (n = 11). Results: The baseline brain parenchymal fraction of the entire cohort was 0.80 ± 0.02 with a mean annual brain volume change of −0.40 ± 0.29%. Univariate analysis demonstrated a higher rate of brain atrophy in older subjects ( p = 0.0001), in those with higher HbA 1c ( p = 0.0001), higher body mass index ( p = 0.02), high alcohol intake ( p = 0.04), severe WMH ( p = 0.03), and in APOE e4 carriers ( p = 0.07). Multivariate analysis suggested that baseline brain parenchymal fraction, HbA 1c , and WMH score explain a major proportion of variance in the rates of brain atrophy in the cohort (corrected R 2 = 0.27; p = 0.0001). Conclusions: Neurologically asymptomatic elderly experience continuing brain volume loss, which appears to accelerate with age. Glycated hemoglobin A (HbA 1c ) was identified as a risk factor for a greater rate of brain atrophy. Clustering of factors associated with the so-called metabolic syndrome in subjects with high HbA 1c suggests a link between this syndrome and late-life brain tissue loss.

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm 3 after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Background: Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)β-1b. Methods: Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFNβ-1–treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFNβ-1b, or statins plus IFNβ-1b. The authors analyzed proliferative activity of T cells and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells. Results: All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFNβ-1b showed a similar effect; statins and IFNβ-1b together added their inhibitory potentials. Furthermore, statins reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects. Conclusions: Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.

Cognitive impairment is increasingly recognized as a significant manifestation of multiple sclerosis (MS) and an impediment to patient quality of life. Now evidence presented by Portaccio et al.1 in this issue of Neurology ® suggests that absence of cognitive impairment may also be an important predictor for benign MS (BMS). To date BMS defines a condition “in which the patient remains fully functional in all neurologic systems 15 years after disease onset” as indicated by an Expanded Disability Status Scale (EDSS) score ≤3.2 This label is given retrospectively and reflects primarily a low level of (motor) disability. More importantly, this definition does not preclude that some of these patients subsequently go on to enter a more active and disabling phase of their disease. Thus clinical features alone appear insufficient to define BMS. Inclusion of imaging findings should be one step forward to better characterize BMS. It would be expected that BMS is associated with a lower rate of lesion accrual and less severe tissue damage within and outside lesions.3 Also lesion distribution such as relative …

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.

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.

MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

Objective: To determine the rate, clinical predictors, and cognitive consequences of MRI white matter hyperintensity evolution over 3 years. Methods: In the setting of the Austrian Stroke Prevention Study, 1.5-T MRI was performed at baseline and at a 3-year follow-up in 273 community-dwelling elderly (mean age, 60 ± 6.1 years) without neuropsychiatric disease. At each visit individuals underwent a structured clinical interview and examination, EKG, echocardiography, extensive laboratory workup, and demanding neuropsychological testing. MR images were read by three independent raters, and the change of white matter hyperintensities from baseline was assessed by direct image comparison. The change was graded as absent, minor, or marked. Minor change was defined as a difference of no more than one to four punctate lesions between both scans. A change was considered to be marked if there was a difference of more than four abnormalities or a transition to early-confluent and confluent lesions. Results: Combined ratings indicated lesion progression in 49 individuals (17.9%). Lesion progression was minor in 27 participants (9.9%) and was marked in 22 (8.1%). Regression of white matter hyperintensities did not occur. Diastolic blood pressure (odds ratio, 1.07/mm Hg) 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 neuropsychological test performance over the observational period. Conclusions: White matter hyperintensities progress in elderly normal subjects. Our data may be used as a reference for future observational and interventional studies on white matter hyperintensity progression in various CNS diseases. The lack of an association between lesion progression and cognitive functioning needs to be explored further.

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 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.

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.

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).

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.

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.