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.

Cerebral corticospinal tract injury resulting from high-voltage electrical shock.

Electrical injuries are becoming more common and are increasingly imaged with advanced technologies, such as MR imaging. However, the MR imaging findings of such injuries remain largely unstudied. We report a high-voltage electrical injury to the cerebral corticospinal tracts and document evolution on serial MR images.

Progressive supranuclear palsy phenotype secondary to CADASIL.

BACKGROUND AND PURPOSE: To report a unique case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy manifesting as a progressive supranuclear palsy phenotype, thereby expanding its recognized presentations. METHODS: Review of the pertinent literature from MEDLINE, cross-referencing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, progressive supranuclear palsy, and parkinsonism. Description of a 60-year-old woman who presented with a several year history of step-wise, progressive parkinsonism secondary to cerebral autosomal dominant arteriopathy. RESULTS: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present with a progressive supranuclear phenotype. CONCLUSION: Parkinsonism, including a progressive supranuclear palsy phenotype, is one of a growing number of recognized ways that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy may present.

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.

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.

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.

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.

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.

Ischemic stroke subtypes : a population-based study of functional outcome, survival, and recurrence.

BACKGROUND AND PURPOSE: There is scant population-based information on functional outcome, survival, and recurrence for ischemic stroke subtypes. METHODS: We identified all residents of Rochester, Minnesota, with a first ischemic stroke from 1985 through 1989 using the resources of the Rochester Epidemiology Project medical records linkage system. After reviewing medical records and imaging studies, we assigned patients to 4 major ischemic stroke categories based on National Institute of Neurological Diseases and Stroke Data Bank criteria: large-vessel cervical or intracranial atherosclerosis with stenosis (ATH, n=74), cardioembolic (CE, n=132), lacunar (LAC, n=72), and infarct of uncertain cause (IUC, n=164). We used the Rankin disability score to assess functional outcome and the Kaplan-Meier product-limit method and Cox proportional hazards regression analysis with bootstrap validation to estimate rates and identify predictors of survival and recurrent stroke among these patients. RESULTS: Rankin disabilities were different across stroke subtypes at the time of stroke and 3 months and 1 year later (P=0.001). LAC was associated with milder deficits compared with other subtypes. Mean follow-up among the 442 patients in the cohort was 3.2 years. Estimated rates of recurrent stroke at 30 days were significantly different (P<0.001): ATH, 18.5% (95% CI 9.4% to 27.5%); CE, 5.3% (95% CI 1.2% to 9.6%); LAC, 1.4% (95% CI 0.0% to 4.1%); and IUC, 3. 3% (95% CI 0.4% to 6.2%). After adjusting for age, sex, and stroke severity, infarct subtype was an independent determinant of recurrent stroke within 30 days (P=0.0006; eg, risk ratio for ATH compared with CE=3.3, 95% CI 1.2 to 9.3) but not long term (P=0.07). Four of 25 recurrent strokes within 30 days were procedure-related, each in patients with ATH. Five-year death rates were significantly different (P<0.001): ATH, 32.2% (95% CI 21.1% to 43.2%); CE, 80.4% (95% CI 73.1% to 87.6%); LAC, 35.1% (95% CI 23.6% to 46.0%); and IUC, 48.6% (95% CI 40.5% to 56.7%). With adjustment for age, sex, cardiac comorbidity, and stroke severity, the subtype of ischemic stroke was an independent determinant of long-term (P=0.018; eg, risk ratio for ATH compared with cardioembolic=0.47, 95% CI 0.29 to 0.77) but not 30-day survival (P=0.2). CONCLUSIONS: Early recurrence rates for ischemic stroke caused by ATH are higher than those for other subtypes and higher than previous non-population-based studies have reported. Some of the increased risk of early recurrence among patients with ATH may be iatrogenic. Patients with LAC have better poststroke functional status than those with other subtypes. Survival is poorest among those with ischemic stroke with a cardiac source of embolism.

Ischemic stroke subtypes: a population-based study of incidence and risk factors.

BACKGROUND AND PURPOSE: There is scant population-based information on incidence and risk factors for ischemic stroke subtypes. METHODS: We identified all 454 residents of Rochester, Minn, with a first ischemic stroke between 1985 and 1989 from the Rochester Epidemiology Project medical records linkage system. We used Stroke Data Bank criteria to assign infarct subtypes after reviewing medical records and brain imaging. We adjusted average annual incidence rates by age and sex to the US 1990 population and compared the age-adjusted frequency of stroke risk factors across ischemic stroke subtypes. RESULTS: Age- and sex-adjusted incidence rates (per 100 000 population) were as follows: large-vessel cervical or intracranial atherosclerosis with >50% stenosis, 27; cardioembolic, 40; lacuna, 25; uncertain cause, 52; other or uncommon cause, 4. Sex differences in incidence rates were detected only for atherosclerosis with stenosis (47 [95% CI, 34 to 61] for men; 12 [95% CI, 7 to 17] for women). There was no difference in prior transient ischemic attack and hypertension among subtypes, and diabetes was not more common among patients with lacunar infarction than other common subtypes. CONCLUSIONS: The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.

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.

Use of nursing home after stroke and dependence on stroke severity: a population-based analysis.

BACKGROUND AND PURPOSE: There are few population-based data available regarding nursing home use after stroke. This study clarifies the use of a nursing home after stroke, as well as its dependence on stroke severity, in a defined population. METHODS: All first stroke events among residents of Rochester, Minn, during 1987-1989 were ascertained, subtyped, and assigned Rankin disability scores (RS) before the event, at maximal deficit, and at specified intervals after stroke. Persons were followed from the date of stroke event to death, emigration from Rochester, or December 31, 1994, in complete community-based medical records and Minnesota Case Mix Review Program data tapes to determine nursing home residency before stroke and at 90 days and 1 year after stroke, proportion of survival days in a nursing home, and cumulative risk of admission to a nursing home. RESULTS: There were 251 cases of first cerebral infarction, 24 intracerebral hemorrhages, and 15 subarachnoid hemorrhages among residents of Rochester during 1987-1989. The maximal deficit RS was 1 or 2 for 62 (25%), RS 3 for 72 (29%), and RS 4 or 5 for 117 (47%) of the cerebral infarct patients. Among patients surviving to 90 days or 1 year after cerebral infarction, 25% were in nursing home at 90 days and 22% at 1 year, respectively. Within these maximal deficit RS categories, the percentages of follow-up time spent in a nursing home during the first post-cerebral infarction year are as follows: RS 1 to 2, 4%; RS 3, 10%; and RS 4 to 5, 54%. Multivariate logistic regression revealed that increasing age and RS 4 to 5 at maximal deficit were independent predictors (P<0.0001) of nursing home residency at 90 days and 1 year after stroke, whereas stroke type was not an independent predictor. At 1 year after cerebral infarction, the Kaplan-Meier estimates of proportion of people with at least 1 nursing home admission were 11% for RS 1 to 2, 22% for RS 3, and 68% for RS 4 to 5. CONCLUSIONS: This study provides unique population-based data regarding the short- and long-term use of a nursing home after stroke and its dependence on stroke severity. More than 50% of people with a severe cerebral infarction are in a nursing home 90 days and 1 year after the stroke, and by 1 year, nearly 70% will have required some nursing home stay. Age and stroke severity are independent predictors of nursing home residency after stroke.

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS).

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention. A population-based study.

BACKGROUND: Complication rates of medical therapy for secondary stroke prevention derived from clinical trials may or may not be applicable to patients with cerebrovascular disease in the general population. OBJECTIVE: To determine complication rates for aspirin, warfarin, and intravenous heparin administered for secondary stroke prevention after first episodes of ischemic stroke, transient ischemic attack, or amaurosis fugax in a community. DESIGN: Population-based historical cohort study. SETTING: Rochester, Minnesota. PATIENTS: All residents of Rochester who, between 1985 and 1989, received aspirin (n = 339) or warfarin (n = 145) within 2 years after first ischemic stroke, transient ischemic attack, or amaurosis fugax or received intravenous heparin (n = 201) within 2 weeks after first ischemic stroke, transient ischemic attack, or amaurosis fugax. MEASUREMENTS: Occurrence of major complications caused by therapy. RESULTS: Twenty aspirin-associated complications (1 fatal) occurred during an average 1.7 years of treatment, 8 warfarin-associated complications occurred during an average 0.7 years of treatment, and 3 heparin-associated complications (1 fatal) occurred during an average 5.1 days of treatment. Complication rates were 3.5 per 100 person-years (95% CI, 2.1 to 5.4) for aspirin, 7.9 per 100 person-years (CI, 3.4 to 15.6) for warfarin, and 0.30 (CI, 0.06 to 0.86) per 100 person-days for heparin. Rates of fatal complications were 0.2 per 100 person-years (CI, 0 to 1.0) for aspirin, 0 per 100 person-years (CI, 0 to 3.6) for warfarin, and 0.10 per 100 person-days (0 to 0.55) for heparin. CONCLUSIONS: Complication rates for warfarin and intravenous heparin given as therapy for secondary stroke prevention in Rochester, Minnesota, were lower than rates reported from earlier trials and observational studies. However, complication rates for warfarin were higher than in more recent referral-based studies and multicenter randomized trials. After adjustment for duration of therapy, complication rates for heparin were higher than those for aspirin or warfarin. These rates can be used to judge the applicability of complication rates derived from ongoing clinical trials.

Incidence of transient ischemic attack in Rochester, Minnesota, 1985-1989.

BACKGROUND AND PURPOSE: There is scant information available on the incidence of transient ischemic attack (TIA) in a defined population. This study defines incidence rates of first TIA and subtypes of TIA during 1985-1989 and compares the incidence to that obtained from a 1960-1972 cohort study. METHODS: Medical records of all residents of Rochester with potential diagnosis of TIA during 1985-1989 were screened to determine whether the case met the criteria for TIA. All available data were used to determine the vascular distribution of the TIA. Average annual age- and sex-adjusted incidence rates were calculated for 1985-1989, and results were compared with incidence rates determined in a Rochester-based 1960-1972 cohort study. RESILTS: Two hundred two cases of first TIA or amaurosis fugax occurred among Rochester residents during 1985-1989. The age- and sex-adjusted incidence rate for any TIA was 68/100 000 population. Incidence of amaurosis fugax was 13/100 000; anterior circulation (cerebral) TIA, 38/100 000; and vertebrobasilar distribution TIA, 14/100 000. Rates were similar to those determined from a 1960-1972 cohort study. CONCLUSIONS: The incidence rate of TIA is 41% that of stroke incidence. TIA incidence in Rochester, Minn, is higher than has been previously reported for other sites throughout the world. Although comparison with prior time periods is difficult because of ascertainment issues, it appears that there has been no significant change in TIA incidence since the decade of the 1960s or earlier. This suggests that the most common mechanism for TIA (atherosclerosis) has not changed in prevalence, nor have risk factors leading to this mechanism.

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.

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.

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.

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.