Susac syndrome: clinical characteristics and treatment in 29 new cases.

BACKGROUND AND PURPOSE: There are few clinical studies on the attempted treatments and outcomes in patients with Susac syndrome (SS) (retinocochleocerebral vasculopathy). METHODS: A retrospective review was performed of all patients presenting with SS at the Mayo Clinic in Rochester, Minnesota, USA (1 January 1998-1 October 2011). RESULTS: There were 29 cases of SS (24 women, mean age at presentation, 35 years; range, 19-65; full triad of brain, eye, and ear involvement, n = 16; mean follow-up time, 29 months). Thirty CSF analyses were performed in 27 cases (mean protein 130 mg/dl, range 35-268; mean cell count 14, range 1-86). MRI of the brain showed corpus callosal involvement (79%), T2-weighted hyperintensities (93%), and gadolinium enhancement (50%). Average lowest modified Rankin Scale score was 2.5 (median 2, range 0-5). Most patients (93%) received immunosuppressive treatment, with a mean time to treatment of 2 months following symptomatic onset. Treatments included intravenous methylprednisolone or dexamethasone (n = 23), oral corticosteroids (n = 24), plasma exchange (PLEX) (n = 9), intravenous immunoglobulin (IVIg) (n = 15), cyclophosphamide (n = 6), mycophenolate mofetil (n = 5), azathioprine (n = 2), and rituximab (n = 1). Most patients also received an antiplatelet agent (n = 21). Improvement or stabilization was noted in eight of 11 cases treated with IVIg in the acute period (three experienced at least partial deterioration) and eight of nine cases of PLEX treatment (one lost to follow up). CONCLUSIONS: Susac syndrome may be severe, disabling, and protracted in some patients. PLEX may be an adjunct or alternative therapy for patients who do not experience symptomatic improvement following steroid treatment.

Predictors of cerebrovascular events and death among patients with valvular heart disease: A population-based study.

BACKGROUND AND PURPOSE: There is little population-based information on cerebrovascular events and survival among valvular heart disease patients. We used the Kaplan-Meier product-limit method and the Cox proportional hazards model to determine rates and predictors of cerebrovascular events and death among valve disease patients. METHODS: This population-based historical cohort study in Olmsted County, Minnesota, reviewed residents with a first echocardiographic diagnosis of mitral stenosis (n=19), mitral regurgitation (n=528), aortic stenosis (n=140), and aortic regurgitation (n=106) between 1985 and 1992. RESULTS: During 2694 person-years of follow-up, 98 patients developed cerebrovascular events and 356 died. Compared with expected numbers, these observations are significantly elevated, with standardized morbidity ratio of 3.2 (95% CI, 2.6 to 3.8) and 2. 5 (95% CI, 2.2 to 2.7), respectively. Independent predictors of cerebrovascular events were age, atrial fibrillation, and severe aortic stenosis. The risk ratio of severe aortic stenosis was 3.5 (95% CI, 1.4 to 8.6), with atrial fibrillation conferring greater risk at younger age. Predictors of death were age, sex, cerebrovascular events, ischemic heart disease, and congestive heart failure, the greatest risk being among those with both congestive heart failure and cerebrovascular events (risk ratio=8.8; 95% CI, 5. 8 to 13.4). Valve disease type and severity were not independent determinants of death. CONCLUSIONS: The risk of cerebrovascular events and death among patients with valve disease remains high. Age, atrial fibrillation, and severe aortic stenosis are independent predictors of cerebrovascular events, and age, sex, cerebrovascular events, congestive heart failure, and ischemic heart disease are independent predictors of death in these patients.

Retinocochleocerebral vasculopathy.

We report 10 patients with retinocochleocerebral vasculopathy and review the clinical and diagnostic considerations in previously reported patients with this uncommonly recognized disease. The clinical manifestations include acute and subacute multifocal and diffuse encephalopathic symptoms, hearing loss, and visual loss attributable to microangiopathy affecting the arterioles of the brain, retina, and cochlea. Diagnosis is facilitated by demonstration of retinal arteriolar occlusions without uveitis or keratoconjunctivitis, mid- to low-frequency unilateral or bilateral sensorineural hearing loss, and numerous small foci of increased signal in the white and gray matter on T2 weighted brain magnetic resonance imaging. Because many conditions may produce any combination of strokelike cerebral symptoms, encephalopathy, hearing loss, and visual loss, the differential diagnosis for retinocochleocerebral vasculopathy includes connective tissue disease, demyelinating disease, procoagulant state, infection, neoplasm, and more routine mechanisms of cerebral and retinal ischemia. Brain biopsy specimens demonstrate only minimal nonspecific periarteriolar chronic inflammatory cell infiltration with or without microinfarcts. The demonstration of subclinical arteriolar microangiopathy in muscle biopsy specimens, documented in 3 of our patients may assist in making the diagnosis. The clinical course appears to be monophasic. In addition to corticosteroids, treatment options include immunosuppressant agents (cyclophosphamide or azathioprine) aspirin, calcium channel blockers (nimodipine), intravenous immunoglobulin, and plasmapheresis. The etiology of the disease is unknown, but histopathologic and laboratory evidence suggests that an immune-mediated mechanism may be involved.

Patent foramen ovale in patients with cerebral infarction. A transesophageal echocardiographic study.

OBJECTIVES: To determine the frequency of patent foramen ovale (PFO) among various subtypes of cerebral infarction. To determine whether any historical or clinical characteristics predict the presence or absence of PFO in these patients. DESIGN: Comorbidity and infarct subtype study. SETTING: Referral-based study. PATIENTS: One hundred sixteen patients with cerebral infarction consecutively referred for transesophageal echocardiography during a 6-month period. MAIN OUTCOME MEASURES: Infarct subtype classification was made using a clinical and radiographic diagnostic rubric similar to that used by the Stroke Data Bank of the National Institute of Neurological Diseases and Stroke. The frequency of various risk factors and clinical characteristics in patients with and in those without PFO and the frequency of PFO in patients with various infarct subtypes were compared (chi 2 or Fisher exact tests). RESULTS: Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P = .03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes mellitus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the same time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P = .08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P = .01). CONCLUSION: Although PFO was overrepresented in patients with infarcts of uncertain in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

Mitral valve prolapse and the risk of stroke after initial cerebral ischemia.

Referral-based studies suggest that patients with cerebral ischemia and mitral valve prolapse are prone to recurrent cerebral ischemic events. Our purpose was to determine the risk of subsequent stroke in a population-based group of patients with ischemic stroke or TIA and mitral valve prolapse. From 1975 through 1990, 49 residents of Olmsted County, MN, had an initial ischemic stroke or TIA and echocardiographically diagnosed mitral valve prolapse. Risk of subsequent stroke in this cohort was compared with the age- and sex-adjusted rates of recurrent stroke after initial cerebral ischemia in the Rochester, MN, population. Mean age of the patients was 72 years. Thirty-one (63%) were women. Nine had subsequent stroke (5.5 per 100 person-years). For Rochester patients who had initial ischemic stroke in the period 1975 through 1984, 10.72 recurrent strokes were expected (relative risk, 0.84; 95% confidence limits, 0.38 to 1.59). For Rochester patients with initial ischemic stroke or TIA in the period 1975 through 1979, 12.31 recurrent strokes were expected (relative risk, 0.73; 95% confidence limits, 0.33 to 1.39). There is no evidence of increased subsequent stroke risk among patients with initial episodes of cerebral ischemia and mitral valve prolapse relative to the age- and sex-adjusted recurrent stroke rates in the community.

Survival and recurrence after first cerebral infarction: a population-based study in Rochester, Minnesota, 1975 through 1989.

We used the Kaplan-Meier product limit method to estimate rates and Cox proportional hazards regression analysis with bootstrap validation to model significant independent predictors of and temporal trends in survival and recurrent stroke among 1,111 residents of Rochester, MN, who had a first cerebral infarction from 1975 through 1989. The risk of death after first cerebral infarction was 7% +/- 0.7% at 7 days, 14% +/- 1.0% at 30 days, 27% +/- 1.3% at 1 year, and 53% +/- 1.5% at 5 years. Independent risk factors for death after first cerebral infarction were age (p < 0.0001), congestive heart failure (p < 0.0001), persistent atrial fibrillation (p < 0.0001), recurrent stroke (p < 0.0001), and ischemic heart disease (p < 0.0001 for age < or =70, p > 0.05 for age >70). The risk of recurrent stroke after first cerebral infarction was 2% +/- 0.4% at 7 days, 4% +/- 0.6% at 30 days, 12% +/- 1.1% at 1 year, and 29% +/- 1.7% at 5 years. Age (p = 0.0002) and diabetes mellitus (p = 0.0004) were the only significant independent predictors of recurrent stroke. Neither the year nor the quinquennium of the first cerebral infarction was a significant determinant of survival or recurrence. The temporal trend toward improving survival after first cerebral infarction documented in Rochester, MN, in the decades before 1975 has ended.

Comparison of population-based models of risk factors for TIA and ischemic stroke.

OBJECTIVE: To determine whether there is a difference in the risk factors for ischemic stroke and for TIA. BACKGROUND: TIA is associated with a high risk for ischemic stroke, but some have considered TIA as mild ischemic stroke. Prevention of disabling stroke is sufficient reason to label TIA as a precursor for stroke, but some risk factors may be more or less associated with TIA than with ischemic stroke, suggesting differences in mechanism. METHODS: The medical records linkage system for the Rochester Epidemiology Project provided the means of identifying first episodes of TIA in the Rochester, MN population among those who had not had ischemic stroke. Control subjects were selected from an enumeration of the population through the medical records. The exposure to various risk factors was ascertained. The conditional likelihood approach to estimate the parameters of a multiple logistic model permitted estimation of the OR for TIA for each risk factor while adjusting for confounding variables. RESULTS: The multivariable logistic regression model for TIA shows that the estimates of the ORs for ischemic heart disease, hypertension, persistent atrial fibrillation, diabetes mellitus, and cigarette smoking are similar to the ORs for those variables in the ischemic stroke model. However, the OR for mitral valve disease in the TIA model is 0.4, suggesting that mitral valve disease is unlikely to be associated with cerebral ischemic episodes that are brief enough to be called TIA.

Ischemic stroke: outcomes, patient mix, and practice variation for neurologists and generalists in a community.

A variety of methods was used to compare patient mix, practice variation, survival, and recurrence after first ischemic stroke among Rochester, MN residents. The significance of the results for neurologists and generalists was examined. Age, stroke severity, congestive heart failure (CHF), and the interaction between atrial fibrillation and patient groups were determinants of survival. Without atrial fibrillation, patients on neurology services and patients on general services with neurology consultation had better survival than those without neurology consultation, adjusting for age, stroke severity, and CHF. With atrial fibrillation, patients on general services with neurology consultation had no better survival compared with those without neurology consultation; patients on neurology services had worse survival (p=0.002). There was no difference in stroke recurrence. Evaluation by a neurologist is associated with better survival for most patients with ischemic stroke but not those with atrial fibrillation. Only a randomized trial can determine whether this association is causal.

Dolichoectasia of the intracranial arteries in patients with first ischemic stroke: a population-based study.

OBJECTIVE: The objective of this study was to estimate the frequency of intracranial arterial dolichoectasia among patients with first ischemic stroke and to compare clinical characteristics, survival, and recurrence in those with and without the abnormality. BACKGROUND: Dolichoectasia may cause cerebral infarction by thrombosis, embolism, stenosis, or occlusion of deep penetrating arteries. METHODS: The chi-square, Fisher's exact, and logrank tests were used to compare clinical characteristics, survival, and recurrence for patients with and without dolichoectasia among the 387 residents of Rochester, MN, who had brain CT or MRI for first cerebral infarction from 1985 through 1989. RESULTS: Twelve patients (3.1%) had dolichoectasia. Patients with dolichoectasia were more likely to have had stroke fitting a clinical and radiographic pattern of lacunar infarction than those without (42% and 17% respectively; p=0.04). Dolichoectasia was detected in the vertebrobasilar system in eight patients (66.7%), in the carotid system in two patients (16.7%), and in both circulatory systems in two patients (16.7%). There were no significant differences in the following characteristics among those with and without dolichoectasia: age, sex, hypertension, diabetes, smoking, and preceding transient ischemic attack. Patients with dolichoectasia had better survival (relative risk [RR] for death, 0.26; p=0.04) after first cerebral infarction but higher rates of stroke recurrence (RR, 2.4; p=0.02). CONCLUSIONS: Dolichoectasia is detected in 38 of patients with first cerebral infarction and is associated with better survival but higher rates of stroke recurrence.

Hemodynamic role of ophthalmic artery collateral in internal carotid artery occlusion.

We performed duplex and transcranial Doppler studies in 36 patients with angiographically documented internal carotid artery occlusion (ICAO) to determine the effect of ophthalmic artery collateral (OAC) on measures of vascular resistivity both proximal and distal to the occlusion. Resistance in the common carotid artery, measured by the resistivity index, was significantly lower in the group with OAC than in those without OAC, indicating a shunt to the low resistance intracranial circuit. The pulsatility index (PI) of the Doppler signal in the ipsilateral middle cerebral artery, a measure of both inflow pressure and distal vascular resistance, did not differ between those with and without OAC. However, the presence of circle of Willis collateral pathways (anterior communicating and/or posterior communicating artery) did appear to have a significant effect on pulsatility. When both were present angiographically, PI was higher than in the group with only 1 Willisian collateral. These findings suggest that OAC has a marginal effect on vascular resistance in arterial bed distal to an ICAO, while Willisian collaterals appear to have a more important role in cerebral perfusion, as measured indirectly by Doppler methods.

The role of transcranial Doppler in confirming brain death: sensitivity, specificity, and suggestions for performance and interpretation.

We performed transcranial Doppler (TCD) examinations on 54 comatose patients over a 1-year period. Of 49 patients with technically adequate TCD examinations, 23 met criteria for determination of brain death by clinical and EEG criteria (21) or clinical criteria alone (2; EEG not performed). A TCD waveform abnormality, consisting of absent or reversed diastolic flow, or small early systolic spikes, in at least 2 intracranial arteries, occurred in 21 brain-dead patients, but in none of the other patients in coma. With appropriate guidelines for performance and interpretation, TCD could be incorporated into institutional protocols as a rapid and convenient alternative to EEG for confirmation of brain death.

Cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia.

We describe two women (ages 35 and 36 years) with cerebral ischemia, hepatitis C virus, and mixed cryoglobulinemia. One patient (case 1) was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1, and middle cerebral artery M1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type III), hypocomplementemia, and a high positive test result for rheumatoid factor. In the other patient (case 2), cerebral ischemia and seizures developed in the setting of previously documented mixed cryoglobulinemia (type II), membranoproliferative glomerulonephritis, and hypocomplementemia. In this patient, a brain biopsy demonstrated cerebral infarction. Hepatitis C virus infection was confirmed in both patients by polymerase chain reaction detection of hepatitis C virus RNA. These two cases document the occurrence of cerebral ischemia in patients with hepatitis C virus infection and mixed cryoglobulinemia. Testing for hepatitis C virus and cryoglobulins should be considered in selected patients with cerebral ischemia of inobvious cause.

Transcranial Doppler ultrasonography: clinical applications in cerebrovascular disease.

Transcranial Doppler ultrasonography was introduced in 1982 as a noninvasive procedure for assessment of the intracranial cerebral circulation. The lightweight and portable equipment used for transcranial Doppler examination facilitates its use in the bedside assessment of critically ill hospitalized patients and outpatients. Clinical applications include the diagnosis of vasospasm in patients with subarachnoid hemorrhage, assessment of intracranial collateral flow in patients with extracranial arterial occlusive disease, detection of intracranial arterial stenosis, identification of the feeding arteries of arteriovenous malformations and monitoring the hemodynamic effects of their treatment, confirmation of the clinical diagnosis of brain death, intensive-care unit monitoring of brain-injured patients, and intraoperative and postoperative monitoring of neurosurgical patients. Transcranial Doppler technology is also providing new insights into the pathophysiologic mechanisms of a variety of cerebrovascular conditions. Clinicians will find transcranial Doppler technology most helpful if they have a specific question about the status of the intracranial circulation. Further investigations may expand the clinical and research utility of this technology.

A population-based study of stroke in the setting of mitral valve prolapse: risk factors and infarct subtype classification.

OBJECTIVE: To determine the frequency of risk factors and the mechanisms of stroke in patients with cerebral infarction and echocardiographically diagnosed mitral valve prolapse in the general population. DESIGN: We conducted a population-based study in Olmsted County, Minnesota, which encompassed the period from 1975 through 1989. MATERIAL AND METHODS: Study subjects were identified by using the Rochester Epidemiology Project medical records-linkage system. Cardiac and neurologic data were summarized, and a two-sided chi 2 test or Fisher's exact test was used for statistical analysis. RESULTS: Among residents of Olmsted County, Minnesota, 33 had echocardiographically diagnosed mitral valve prolapse and a first cerebral infarction between 1975 and 1989. The mean patient age was 71 years, and more than half (52%) were men. Risk factors for stroke included hypertension (55%), smoking (42%), coronary artery disease (27%), atrial fibrillation or flutter (24%), congestive heart failure (21%), hypertensive heart disease (21%), prior myocardial infarction (12%), diabetes (9%), and sick sinus syndrome (3%). Cerebral infarction subtypes were as follows: cardioembolic source (excluding mitral valve prolapse only), 30%; lacuna, 12%; large-vessel atherosclerosis, 9%; other, 6%; and infarction of uncertain cause (including mitral valve prolapse), 42%. CONCLUSION: Most Olmsted County patients with cerebral infarction and echocardiographically diagnosed mitral valve prolapse had other risk factors for stroke, and most had identifiable mechanisms of infarction other than embolism due to mitral valve prolapse.

Recurrence of Susac syndrome (retinocochleocerebral vasculopathy) after remission of 18 years.

Susac syndrome (retinocochleocerebral vasculopathy) is a syndrome of unknown pathogenesis. The triad of multifocal encephalopathy, visual loss, and hearing loss is caused by microangiopathy of the brain, retina, and cochlea. The illness tends to be monophasic, and to our knowledge, recurrence after years of remission has not been reported. We describe a 51-year-old woman with symptoms, signs, and brain magnetic resonance imaging findings consistent with recurrence of Susac syndrome 18 years after remission. Clinicians should be aware of the possibility of late recurrence of Susac syndrome when evaluating patients with a distant history of the syndrome who present with complaints referable to the brain, retina, and cochlea.

Transient ischemic attack and minor ischemic stroke: an algorithm for evaluation and treatment. Mayo Clinic Division of Cerebrovascular Diseases.

OBJECTIVE: To report a cost-effective and scientifically based algorithm for the clinical assessment and treatment of patients with transient ischemic attack (TIA) or minor ischemic stroke. DESIGN: We comprehensively reviewed the literature on the epidemiologic features, assessment approaches, and treatment recommendations for ischemic cerebrovascular disease and developed an algorithm by using the available clinical and research data to support all decision-making steps. MATERIAL AND METHODS: For patients with TIA or minor ischemic stroke, the appropriate setting for investigation (inpatient or outpatient), suggested diagnostic tests, use of anticoagulants and antiplatelet agents, and indications for surgical treatment are reviewed. RESULTS: Although stroke is a common cause of death and lost productivity in the United States, the clinical assessment of patients with TIA or minor ischemic stroke has lacked consistency. The simplified algorithm clarifies patients who may be candidates for hospitalization and possible anticoagulation therapy. Initial diagnostic studies should include computed tomography of the head without use of a contrast agent, which quickly distinguishes nonhemorrhagic from hemorrhagic cerebrovascular disease. Evolving noninvasive studies of the cerebral vasculature are providing increasingly sensitive means of detecting stenoses, yet cerebral angiography remains the "gold standard." Treatment options depend on the pathophysiologic findings on diagnostic evaluation. CONCLUSION: The assessment of patients with ischemic cerebrovascular disease is complex. The simplified algorithmic approach reported herein necessitates entry of appropriate patients into the algorithm. Because of clinical heterogeneity, an algorithm may apply to a wide spectrum of patients but will not cover every situation; hence, evaluation must be guided by a patient's unique history and findings on examination and by the physician's clinical experience.

Patent foramen ovale transcatheter closure device thrombosis.

The role of patent foramen ovale (PFO) in patients with cryptogenic stroke (stroke of unknown cause) remains controversial, although an association seems likely in younger patients with atrial septal aneurysms and PFO. The mechanism of cryptogenic stroke in these patients is presumed to be paradoxical embolism via right-to-left shunt across the PFO. The available options for treatment include medical therapy with antiplatelet or anticoagulant therapy or closure of the PFO surgically or with use of transcatheter PFO closure devices. We describe 2 cases of bilateral device thrombosis associated with use of a transcatheter PFO closure device (CardioSEAL). To our knowledge, only 1 other case of thrombosis associated with use of this device has been reported.

Hyperhomocysteinemia in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

OBJECTIVE: To determine whether patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) had evidence of increased homocysteine levels compared with non-CADASIL patients with ischemic stroke or transient ischemic attack. PATIENTS AND METHODS: We compared fasting plasma homocysteine levels and levels 6 hours after oral loading with methionine, 100 mg/kg, in non-CADASIL patients with ischemic stroke or transient ischemic attack and in patients with CADASIL. Prechallenge, postchallenge, and change in homocysteine levels between the 2 groups were compared with use of the Wilcoxon rank sum test. RESULTS: CADASIL and non-CADASIL groups were similar in age (mean, 48.8 vs. 46.5 years, respectively; 2-tailed t test, P=.56) and sex (men, 86% vs 59%; Fisher exact test, P=.12). The 59 patients in the CADASIL group had higher median plasma homocysteine levels compared with the 14 patients in the non-CADASIL group, both in the fasting state (12.0 vs 9.0 micromol/L; P=.03) and after methionine challenge (51.0 vs 34.0 micromol/L; P=.007). Median difference between homocysteine levels before and after methionine challenge was greater in the CADASIL group than in the non-CADASIL group (34.5 vs. 24.0 micromol/ L; P = .02). CONCLUSION: Our findings raise the possibility that increased homocysteine levels or abnormalities of homocysteine metabolism may have a role in the pathogenesis of CADASIL.

Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women.

OBJECTIVE: To evaluate the contribution of left atrial (LA) volume in predicting atrial fibrillation (AF). PATIENTS AND METHODS: In this retrospective cohort study, a random sample of 2200 adults was identified from all Olmsted County, Minnesota, residents who had undergone transthoracic echocardiographic assessment between 1990 and 1998 and were 65 years of age or older at the time of examination, were in sinus rhythm, and had no history of AF or other atrial arrhythmias, stroke, pacemaker, congenital heart disease, or valve surgery. The LA volume was measured off-line by using a biplane area-length method. Clinical characteristics and the outcome event of incident AF were determined by retrospective review of medical records. Echocardiographic data were retrieved from the laboratory database. From this cohort, 1655 patients in whom LA size data were available were followed from baseline echocardiogram until development of AF or death. The clinical and echocardiographic associations of AF, especially with respect to the role of LA volume in predicting AF, were determined. RESULTS: A total of 666 men and 989 women, mean +/- SD age of 75.2 +/- 7.3 years (range, 65-105 years), were followed for a mean +/- SD of 3.97 +/- 2.75 years (range, < 1.00-10.78 years); 189 (11.4%) developed AF. Cox model 5-year cumulative risks of AF by quartiles of LA volume were 3%, 12%, 15%, and 26%, respectively. With Cox proportional hazards multivariate models, logarithmic LA volume was an independent predictor of AF, incremental to clinical risk factors. After adjusting for age, sex, valvular heart disease, and hypertension, a 30% larger LA volume was associated with a 43% greater risk of AF, incremental to history of congestive heart failure (hazard ratio [HR], 1.887; 95% confidence interval [CI], 1.230-2.895; P = .004), myocardial infarction (HR, 1.751; 95% CI, 1.189-2.577; P = .004), and diabetes (HR, 1.734; 95% CI, 1.066-2.819; P = .03). Left atrial volume remained incremental to combined clinical risk factors and M-mode LA dimension for prediction of AF (P < .001). CONCLUSION: This study showed that a larger LA volume was associated with a higher risk of AF in older patients. The predictive value of LA volume was incremental to that of clinical risk profile and conventional M-mode LA dimension.

Fatal or severely disabling cerebral infarction during hospitalization for stroke or transient ischemic attack.

Six (1%) of 578 patients admitted for cerebral infarction or transient ischemic attack (TIA) suffered a fatal or severely disabling in-hospital cerebral infarction following a period of stabilization or improvement lasting more than 1 day. These infarctions were characterized by the sudden onset of stupor or coma and subsequent development of transtentorial herniation due to carotid or middle cerebral artery territory infarction, or widespread brain-stem infarction due to basilar occlusion. Only one patient survived. Four patients had large-vessel disease documented by Doppler, angiography, or at autopsy. Each of these six infarcts occurred during the morning hours, 4-9 days after the initial event, 3-8 days after initiation of intravenous heparin, and within 4-8 h after intravenous heparin had been discontinued. No coagulation abnormalities were documented. We believe that these cases indicate that among patients admitted for cerebral infarction or TIA, fatal or severely disabling in-hospital cerebral infarction after a period of stabilization or improvement may occur in patients having an initially mild to moderate clinical deficit, that those suffering large artery disease may be at greater risk, and that there may be a relationship between heparin withdrawal and cerebral infarction in some patients.