Primary central nervous system vasculitis mimicking brain tumor: Comprehensive analysis of 13 cases from a single institutional cohort of 191 cases.

OBJECTIVE: To describe the clinical, laboratory, and imaging features and course of patients with primary central nervous system vasculitis (PCNSV) presenting with an intracranial tumor-like mass (TLM). METHODS: We retrospectively studied a cohort of 191 consecutive patients with PCNSV seen at the Mayo Clinic, Rochester, MN over a 35-year period (1982-2017). 13/191 patients presented with a TLM. We compared the findings in these 13 patients with those from the 178 without this presentation. RESULTS: In 13 of 191 (6.8%) patients with TLM the diagnosis of PCNSV was established by cerebral biopsy. Granulomatous vasculitis was found in 11/13 patients, accompanied by vascular deposits of ß-amyloid peptide in 7. Compared to the 178 patients without TLM, the patients with TLM were more likely to be male (p = 0.04), and less likely to have a transient ischemic attack (p = 0.023), bilateral cerebral infarcts (p = 0.018), or vasculitic lesions on angiography (p = 0.045). They were more likely to have seizures (p = 0.022), gadolinium-enhanced lesions (p = 0.007), and amyloid angiopathy (p = 0.046). All 13 patients responded to therapy and 8/13 (61.5%) had a Rankin disability score of 0 at last visit. Overall, high disability scores (Rankin scores 4-6) at last follow-up were associated with increasing age (odds ratio, OR, 1.49) and cerebral infarction (OR, 3.47), but were less likely in patients with gadolinium-enhanced lesions (OR, 0.36) and amyloid angiopathy (OR, 0.21). CONCLUSION: In PCNSV a TLM at presentation represents a definable subgroup of patients with a favourable treatment response.

Primary central nervous system vasculitis with intracranial aneurysm.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are rarely reported in primary central nervous system vasculitis (PCNSV). In this study we described the clinical findings, response to therapy, and outcomes of UIA in a large cohort of PCNSV patients. METHODS: We retrospectively studied 216 consecutive patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 40-year period. UIAs were identified on cerebral angiography. The clinical, laboratory, radiologic and pathologic findings, management, and outcomes of patients with UIA were described and compared with those without UIA. RESULTS: 12/216 (5.5 %) PCNSV patients had at least one UIA. Two patients underwent biopsies; one yielded negative results, while the other showed necrotizing vasculitis. Eleven patients had evidence of UIA on angiogram at diagnosis. One patient developed an aneurysm during the follow-up associated with a worsening of vasculitic radiological findings. The most common presenting symptom for PCNSV in the setting of UIA was headache (67 %), followed by persistent neurologic deficit or stroke (50 %). Most patients with UIA presented with multiple cerebral infarcts on MRI (67 %), one patient had subarachnoid hemorrhage, and one left parieto-occipital intracerebral hematoma, both unrelated to the aneurysm. Black blood imaging was performed in 4 patients and 2 showed segmental circumferential mural enhancement involving multiple vessels. Two patients had 2 UIAs, while the other 10 had 1. The most frequent UIA location was internal carotid artery (50 %), followed by anterior cerebral artery (21 %). Ten of the UIAs were < 5 mm in diameter, and 3 were 5-7 mm in diameter; the size was not available for one. All UIAs were unchanged in size and configuration during follow-up (median: 18.5 months; range 1-151 months) and no new aneurysms were detected. Compared to the 204 patients with PCNSV without a UIA, no significant clinical differences were observed, except for a reduced disability at last follow-up (p = 0.038). CONCLUSIONS: UIAs uncommonly occur in PCNSV.

Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study.

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies), and Parkinson disease (PD). There are no data on such risks in a population-based sample. METHODS: Cognitively normal subjects aged 70 to 89 years in a population-based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15-month intervals. In a Cox proportional hazards model, we measured the risk of developing MCI, dementia, and PD among the exposed (probable RBD [pRBD](+)) and unexposed (pRBD(-)) cohorts. RESULTS: Forty-four subjects with pRBD(+) status at enrollment (median duration of pRBD features was 7.5 years) and 607 pRBD(-) subjects were followed prospectively for a median of 3.8 years. Fourteen of the pRBD(+) subjects developed MCI, and 1 developed PD (15/44 = 34% developed MCI/PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD(+) subjects were at increased risk of MCI/PD (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.3-3.9; p = 0.005). Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication-associated RBD. Duration of pRBD symptoms did not predict the development of MCI/PD (HR, 1.05 per 10 years; 95% CI, 0.84-1.3; p = 0.68). INTERPRETATION: In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI/PD over 4 years.

Subtle gait changes in patients with REM sleep behavior disorder.

Many people with rapid eye movement (REM) sleep behavior disorder (RBD) have an underlying synucleinopathy, the most common of which is Lewy body disease. Identifying additional abnormal clinical features may help in identifying those at greater risk of evolving to a more severe syndrome. Because gait disorders are common in the synucleinopathies, early abnormalities in gait in those with RBD could help in identifying those at increased risk of developing overt parkinsonism and/or cognitive impairment. We identified 42 probable RBD subjects and 492 controls using the Mayo Sleep Questionnaire and assessed gait velocity, cadence, and stride dynamics with an automated gait analysis system. Cases and controls were similar in age (79.9 ± 4.7 and 80.1 ± 4.7, P = 0.74), Unified Parkinson's Disease Rating Scale Part III (UPDRS) score (3.3 ± 5.5 and 1.9 ± 4.1, P = 0.21) and Mini-Mental State Examination scores (27.2 ± 1.9 and 27.7 ± 1.6, P = 0.10). A diagnosis of probable RBD was associated with decreased velocity (-7.9 cm/s; 95% confidence interval [CI], -13.8 to -2.0; P < 0.01), cadence (-4.4 steps/min; 95% CI, -7.6 to -1.3; P < 0.01), significantly increased double limb support variability (30%; 95% CI, 6-60; P = 0.01), and greater stride time variability (29%; 95% CI, 2-63; P = 0.03) and swing time variability (46%; 95% CI, 15-84; P < 0.01). Probable RBD is associated with subtle gait changes prior to overt clinical parkinsonism. Diagnosis of probable RBD supplemented by gait analysis may help as a screening tool for disorders of α-synuclein.

Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study.

BACKGROUND: Bleeding events are the major obstacle to the widespread use of warfarin for secondary stroke prevention. Previous studies have not examined the use of risk stratification scores to estimate lifetime bleeding risk associated with warfarin treatment in a population-based setting. The purpose of this study is to determine the lifetime risk of bleeding events in ischemic stroke patients with atrial fibrillation (AF) undergoing warfarin treatment in a population-based cohort and to evaluate the use of bleeding risk scores to identify patients at high risk for lifetime bleeding events. METHODS: The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with AF undergoing warfarin treatment for secondary stroke prevention from 1980 to 1994. Medical information for patients seen at Mayo Clinic and at Olmsted Medical Center was used to retrospectively risk-stratify stroke patients according to bleeding risk scores (including the HAS-BLED and HEMORR2HAGES scores) before warfarin initiation. These scores were reassessed 1 and 5 years later and compared with lifetime bleeding events. RESULTS: One hundred patients (mean age, 79.3 years; 68% women) were studied. Ninety-nine patients were observed until death. Major bleeding events occurred in 41 patients at a median of 19 months after warfarin initiation. Patients with a history of hemorrhage before warfarin treatment were more likely to develop major hemorrhage (15% versus 3%, P = .04). Patients with baseline HAS-BLED scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (53% versus 7%, P < .01), whereas those with HEMORR2HAGES scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (52% versus 16%, P = .03). Patients with an increase in the HAS-BLED and HEMORR2HAGES scores during follow-up had a higher remaining lifetime risk of major bleeding events compared with those with no change. CONCLUSIONS: Our findings indicate high lifetime bleeding risk associated with warfarin treatment for patients with ischemic stroke. Risk stratification scores are useful to identify patients at high risk of developing bleeding complications and should be recalculated at regular intervals to evaluate the bleeding risk in anticoagulated patients with ischemic stroke.

Primary central nervous system vasculitis presenting with intracranial hemorrhage.

OBJECTIVE: To describe a subset of cases in a large retrospectively identified cohort of patients with primary central nervous system vasculitis (PCNSV) who present with intracranial hemorrhage. METHODS: The study consisted of a cohort of 131 consecutive patients with PCNSV who were seen at the Mayo Clinic over a 25-year period from 1983 to 2007. The diagnosis of PCNSV was based on findings of brain or spinal cord biopsy, cerebral angiography, or both. Intracranial hemorrhage at presentation was defined as the presence of intracerebral or subarachnoid hemorrhage on computed tomography or magnetic resonance imaging (MRI) of the brain within 3 months of the date of PCNSV diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy, and outcomes in patients presenting with intracranial hemorrhage were compared with those without intracranial hemorrhage. RESULTS: Sixteen patients (12.2%) had evidence of intracranial hemorrhage at or near the time of diagnosis. Twelve patients had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. Twelve patients were diagnosed by findings on angiography and 4 by findings on CNS biopsy. Compared with the 115 patients without intracranial hemorrhage, the 16 patients presenting with intracranial hemorrhage were more frequently women, less frequently had altered cognition, a persistent neurologic deficit, or stroke at presentation, less frequently had MRI evidence of cerebral infarctions, and less frequently needed therapy at last followup. A necrotizing histopathologic pattern of vasculitis was observed in 3 of the 4 patients with positive biopsy findings (75%). CONCLUSION: Our findings suggest that intracranial hemorrhage may not be an infrequent occurrence in early PCNSV. Necrotizing vasculitis may be a predominant histopathologic pattern.

Incidence and predictors of myocardial infarction after transient ischemic attack: a population-based study.

BACKGROUND AND PURPOSE: Coronary artery disease is the leading cause of death after TIA. Reliable estimates of the risk of MI after TIA, however, are lacking. METHODS: Our purpose was to determine the incidence of and risk factors for MI after TIA. We cross-referenced preexisting incidence cohorts from the Rochester Epidemiology Project for TIA (1985-1994) and MI (1979-2006) to identify all community residents with incident MI after incident TIA. Incidence of MI after TIA was determined using Kaplan-Meier life-table methods. This was compared to the age-, sex-, and period-specific MI incidences in the general population. Proportional hazards regression analysis was used to examine associations between clinical variables and the occurrence of MI after TIA. RESULTS: Average annual incidence of MI after TIA was 0.95%. Relative risk for incident MI in the TIA cohort compared to the general population was 2.09 (95% CI, 1.52-2.81). This was highest in patients younger than 60 years old (relative risk, 15.1; 95% CI, 4.11-38.6). Increasing age (hazard ratio, 1.51 per 10 years; 95% CI, 1.14-2.01), male sex (hazard ratio, 2.19; 95% CI, 1.18-4.06), and the use of lipid-lowering therapy at the time of TIA (hazard ratio, 3.10; 95% CI, 1.20-8.00) were independent risk factors for MI after TIA. CONCLUSIONS: Average annual incidence of MI after TIA is ≈1%, approximately double that of the general population. The relative risk increase is especially high in patients younger than 60 years old. These data are useful for identifying subgroups of patients with TIA at highest risk for subsequent MI.

Rapidly progressive primary central nervous system vasculitis.

OBJECTIVE: To describe a subset of cases in a large cohort of patients with primary CNS vasculitis (PCNSV) who appear to have a rapidly progressive clinical course. METHOD: In the present study, we use our updated cohort of 131 consecutive patients with PCNSV seen over the 25-year period of 1983-2007 at Mayo Clinic, Rochester, MN, USA. The diagnosis of PCNSV was based on brain/spinal cord biopsy or cerebral angiography. The modified Rankin scale was used to identify rapidly progressive disease and included patients with Rankin scores indicating severe disability or death at diagnosis or within 6 months after the diagnosis. We compared patients with rapidly progressive disease to those without. RESULTS: Compared with the 120 patients without rapidly progressive vasculitis, the 11 patients with rapidly progressive vasculitis more frequently had paraparesis/quadriparesis at presentation, angiographic presence of bilateral, large-vessel vasculitis and MRI evidence of cerebral infarctions; those infarctions were more frequently multiple and bilateral, and more frequently involved both the cortex and subcortical regions on initial MRI. Granulomatous and/or necrotizing histopathological patterns of vasculitis were observed in patients with positive biopsies. CONCLUSION: Rapidly progressive PCNSV appears to form a subset of PCNSV at the worst end of the clinical spectrum of this vasculitis, characterized by bilateral, multiple, large cerebral vessel lesions and multiple CNS infarctions.

Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study.

The authors investigated whether engaging in cognitive activities is associated with aging and mild cognitive impairment (MCI) in a cross-sectional study derived from an ongoing population-based study of normal cognitive aging and MCI in Olmsted County, MN. A random sample of 1,321 study participants ages 70 to 89 (N=1,124 cognitively normal persons, and N=197 subjects with MCI) were interviewed about the frequency of cognitive activities carried out in late life (within 1 year of the date of interview). Computer activities; craft activities, such as knitting, quilting, etc.; playing games; and reading books were associated with decreased odds of having MCI. Social activities, such as traveling, were marginally significant. Even though the point-estimates for reading magazines, playing music, artistic activities, and group activities were associated with reduced odds of having MCI, none of these reached statistical significance. The equally high prevalence of reading newspapers in both groups yielded no significant between-group difference.

Validation of the telephone interview for cognitive status-modified in subjects with normal cognition, mild cognitive impairment, or dementia.

BACKGROUND: The telephone assessment of cognitive functions may reduce the cost and burden of epidemiological studies. METHODS: We validated the Telephone Interview for Cognitive Status-modified (TICS-m) using an extensive in-person assessment as the standard for comparison. Clinical diagnoses of normal cognition, mild cognitive impairment (MCI), or dementia were established by consensus of physician, nurse, and neuropsychological assessments. RESULTS: The extensive in-person assessment classified 83 persons with normal cognition, 42 persons with MCI, and 42 persons with dementia. There was considerable overlap in TICS-m scores among the three groups. Receiver operating characteristic curves identified < or = 31 as the optimal cutoff score to separate subjects with MCI from subjects with normal cognition (sensitivity = 71.4%; subjects with dementia excluded), and < or = 27 to separate subjects with dementia from subjects with MCI (sensitivity = 69.0%; subjects with normal cognition excluded). The TICS-m performed well when subjects with MCI were pooled either with subjects with dementia (sensitivity = 83.3%) or with subjects with normal cognition (sensitivity = 83.3%). CONCLUSIONS: Although the TICS-m performed well when using a dichotomous classification of cognitive status, it performed only fairly in separating MCI from either normal cognition or dementia. The TICS-m should not be used as a free-standing tool to identify subjects with MCI, and it should be used with caution as a tool to detect dementia.

Vegetables, unsaturated fats, moderate alcohol intake, and mild cognitive impairment.

BACKGROUND/AIMS: To investigate associations of the Mediterranean diet (MeDi) components and the MeDi score with mild cognitive impairment (MCI). METHODS: Participants (aged 70-89 years) were clinically evaluated to assess MCI and dementia, and completed a 128-item food frequency questionnaire. RESULTS: 163 of 1,233 nondemented persons had MCI. The odds ratio of MCI was reduced for high vegetable intake [0.66 (95% CI = 0.44-0.99), p = 0.05] and for high mono- plus polyunsaturated fatty acid to saturated fatty acid ratio [0.52 (95% CI = 0.33-0.81), p = 0.007], adjusted for confounders. The risk of incident MCI or dementia was reduced in subjects with a high MeDi score [hazard ratio = 0.75 (95% CI = 0.46-1.21), p = 0.24]. CONCLUSION: Vegetables, unsaturated fats, and a high MeDi score may be beneficial to cognitive function.

Long-term remission, relapses and maintenance therapy in adult primary central nervous system vasculitis: A single-center 35-year experience.

OBJECTIVES: To evaluate long-term treatment and outcomes of patients with primary central nervous system vasculitis (PCNSV). METHODS: In this cohort of 191 consecutive patients with PCNSV seen at Mayo Clinic, Rochester, MN, over 35 years with long-term follow-up we analyzed response to and duration of therapy, frequency of relapses, long-term remission, efficacy of maintenance therapy and initial intravenous glucocorticoid (GC) pulses, survival and degree of disability. We also compared the efficacy of initial IV and oral cyclophosphamide (CYC). RESULTS: A favorable initial response was observed in 83% of patients treated with prednisone (PDN) alone, 81% of those treated with PDN and CYC and 95% of those initially treated with PDN and an immunosuppressant other than CYC. One or more relapses were observed in 30% of patients, 35% had discontinued therapy by last follow-up, and 21.5% maintained remission for at least 12 months after discontinuing therapy. Maintenance therapy was prescribed in 19% of all patients and 34% of patients initially treated with CYC and PDN. High disability scores (Rankin 4-6) and deaths were less frequently observed in patients receiving maintenance therapy and more frequently in patients with Aß-related angiitis. Large vessel involvement and cerebral infarction at diagnosis were associated with a poor treatment response. Aspirin use was positively associated with long-term remission and having gadolinium-enhanced cerebral lesions or meninges was negatively associated. A high disability score at last follow-up and higher mortality rate were associated with increasing age, cerebral infarction and cognitive dysfunction at diagnosis. Lymphocytic vasculitis on biopsy was associated with a more benign course with reduced disability and mortality. Patients initially treated with mycophenolate mofetil had better outcomes compared to those treated with CYC and PDN. No therapeutic advantages were observed in the patients initially treated with intravenous GC pulses. Intravenous and oral CYC were equally effective in inducing the remission. CONCLUSIONS: The majority of patients with PCNSV responded to treatment. We found patient subsets with different outcomes. Mycophenolate mofetil may be an effective alternative to CYC.

Validation and refinement of the ABCD2 score: a population-based analysis.

BACKGROUND AND PURPOSE: Transient ischemic attacks are a frequent diagnosis in the emergency department setting, yet expert opinion as to the proper follow-up and need for hospitalization differs widely. Recently, an effort has been made to risk-stratify patients presenting with transient ischemic attacks through scoring systems such as the ABCD and ABCD2 scales. The aim of our study was to independently validate these scores using a population-based cohort. METHODS: Using the data from the Rochester Stroke and Transient Ischemic Attack Registry and resources of the Rochester Epidemiology Project, medical records of all residents of Rochester, Minn, with a diagnosis of incident transient ischemic attack from 1985 through 1994 were examined (N=284). Patients were scored on the ABCD and ABCD2 scales and new scores were created by adding hyperglycemia and a history of hypertension. The end points of stroke and death were collected previously and were verified through the Rochester Epidemiology Project data. RESULTS: Although our study did find that scores >4 had a statistically significant predictive value for future stroke, a substantial proportion of strokes within 7 days (9 of 36 cases [25%]) occurred in patients with low or intermediate risk scores (< or =4) on the ABCD2 scale. Including history of hypertension and hyperglycemia on presentation increased the sensitivity of the score to identify patients who had a stroke within 7 days. CONCLUSIONS: Reliance on the ABCD and ABCD2 scores misses some patients who will have a stroke within 7 days of a transient ischemic attack. Adding hyperglycemia and a history of hypertension to the predictive model could be useful, but the value of these additions need to be evaluated further.

Should clinicians deliver decision aids? Further exploration of the statin choice randomized trial results.

BACKGROUND: Statin Choice is a decision aid about taking statins. The optimal mode of delivering Statin Choice (or any other decision aid) in clinical practice is unknown. METHODS: To investigate the effect of mode of delivery on decision aid efficacy, the authors further explored the results of a concealed 2 x 2 factorial clustered randomized trial enrolling 21 endocrinologists and 98 diabetes patients and randomizing them to 1) receive either the decision aid or pamphlet about cholesterol, and 2) have these delivered either during the office visit (by the clinician) or before the visit (by a researcher). We estimated between-group differences and their 95% confidence intervals (CI) for acceptability of information delivery (1-7), knowledge about statins and coronary risk (0-9), and decisional conflict about statin use (0-100) assessed immediately after the visit. Follow-up was 99%. RESULTS: The relative efficacy of the decision aid v. pamphlet interacted with the mode of delivery. Compared with the pamphlet, patients whose clinicians delivered the decision aid during the office visit showed significant improvements in knowledge (difference of 1.6 of 9 questions, CI 0.3, 2.8) and nonsignificant trends toward finding the decision aid more acceptable (odds ratio 3.1, CI 0.9, 11.2) and having less decisional conflict (difference of 7 of 100 points, CI -4, 18) than when a researcher delivered the decision aid just before the office visit. CONCLUSIONS: Delivery of decision aids by clinicians during the visit improves knowledge and shows a trend toward better acceptability and less decisional conflict.

A treatment decision aid may increase patient trust in the diabetes specialist. The Statin Choice randomized trial.

AIMS: Decision aids in practice may affect patient trust in the clinician, a requirement for optimal diabetes care. We sought to determine the impact of a decision aid to help patients with diabetes decide about statins (Statin Choice) on patients' trust in the clinician. METHODS: We randomized 16 diabetologists and 98 patients with type 2 diabetes referred to a subspecialty diabetes clinic to use the Statin Choice decision aid or a patient pamphlet about dyslipidaemia, and then to receive these materials from either the clinician during the visit or a researcher prior to the visit. Providers and patients were blinded to the study hypothesis. Immediately after the clinical encounter, patients completed a survey including questions on trust (range 0 to total trust = 100), knowledge, and decisional conflict. Researchers reviewed videotaped encounters and assessed patient participation (using the OPTION scale) and visit length. RESULTS: Overall mean trust score was 91 (median 97.2, IQR 86, 100). After adjustment for patient characteristics, results suggested greater total trust (trust = 100) with the decision aid [odds ratio (OR) 1.77, 95% CI 0.94, 3.35]. Total trust was associated with knowledge (for each additional knowledge point, OR 1.3, 95% CI 1.1, 1.6), patient participation (for each additional point in the OPTION scale, OR 1.1, 95% CI 1.1, 1.2), and decisional conflict (for every 5-point decrease in conflict, OR 1.5, 95% CI 1.2, 1.9). Total trust was not associated with visit length, which the decision aid did not significantly affect. There was no significant effect interaction across the trial factors. CONCLUSIONS: Preliminary evidence suggests that decision aids do not have a large negative impact on trust in the physician and may increase trust through improvements in the decision-making process.

Association of C-reactive protein with mild cognitive impairment.

BACKGROUND: Inflammation is proposed to play a role in the development of Alzheimer's disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample. METHODS: Olmsted County, MN, residents aged 70-89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis alpha (TNFalpha), and adiponectin were measured at baseline. RESULTS: Among 313 subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00-2.01) and with nonamnestic MCI (OR, 2.05; 95% CI, 1.12-3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81-1.82). No association was observed with the other inflammatory markers. CONCLUSIONS: Plasma CRP is associated with prevalent MCI and with nonamnestic MCI in elderly, nondemented persons in a population-based setting. These findings suggest the involvement of inflammation in the pathogenesis of MCI.

Rituximab therapy for primary central nervous system vasculitis: A 6 patient experience and review of the literature.

OBJECTIVES: To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). METHODS: We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. RESULTS: The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17-68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0-4) was lower than that prior to treatment (median 3; range 1-5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p = .006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. CONCLUSIONS: Our data support a potential role for RTX treatment in selected patients with PCNSV.

Primary central nervous system vasculitis: analysis of 101 patients.

OBJECTIVE: To analyze the clinical findings, response to therapy, outcome, and incidence of primary central nervous system vasculitis (PCNSV) in a large cohort from a single center. METHODS: We retrospectively studied 101 patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 21-year period. This was a collaborative study by five departments at a large multispecialty clinic. Clinical findings and outcomes were compared among patients categorized by method of diagnosis, response to therapy, survival, and degree of disability. An annual incidence rate was calculated. RESULTS: Seventy patients were diagnosed by angiography and 31 by central nervous system biopsy. Three histological patterns were observed during biopsy. Although most patients responded to therapy, an increased mortality rate was observed. Relapses occurred in one fourth of patients. Mortality rate and disability at last follow-up were greater in those who presented with a focal neurological deficit, cognitive impairment, cerebral infarctions, and angiographic large-vessel involvement but were lower in those with prominent gadolinium-enhanced lesions when evaluated by magnetic resonance imaging. The annual incidence rate of PCNSV was 2.4 cases per 1,000,000 person-years. INTERPRETATION: PCNSV is a rare disease that may result in serious neurological outcomes or death. Angiography and brain biopsy may complement each other when determining the diagnosis. Early recognition and treatment may reduce poor outcomes. PCNSV is a variable syndrome that appears to consist of several subsets of heterogeneous diseases.

Folate receptor alpha as a tumor target in epithelial ovarian cancer.

OBJECTIVES: Folate receptor alpha (FRalpha) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRalpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease. METHODS: FRalpha expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRalpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death. RESULTS: FRalpha expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRalpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FRalpha staining. FRalpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses. CONCLUSION: FRalpha expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRalpha expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.

Helping patients with type 2 diabetes mellitus make treatment decisions: statin choice randomized trial.

BACKGROUND: Poor quality of information transfer about the benefits and risks of statin drug use may result in patients not making informed decisions that they can act on in a timely fashion. METHODS: The effect of a decision aid about statin drugs on treatment decision making in 98 patients with diabetes was determined in a cluster randomized trial of decision aid vs control pamphlet, with concealed allocation, blinding of participants to study goals, and adherence to the intention-to-treat principle. Twenty-one endocrinologists conducted specialty outpatient metabolic consultations. Patients in the intervention group received Statin Choice, a tailored decision aid that presents the estimated 10-year cardiovascular risk, the absolute risk reduction with use of statin drugs, and the disadvantages of using statin drugs. Patients in the control group received the institution's pamphlet about cholesterol management. We measured acceptability, knowledge about options and cardiovascular risk, and decisional conflict immediately after the visit, and adherence to pill taking was measured 3 months later. RESULTS: Patients favored using the decision aid (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.9); patients who received the decision aid (n = 52) knew more (difference, 2.4 of 9 points; 95% CI, 1.5-3.3), had better estimated cardiovascular risk (OR, 22.4; 95% CI, 5.9-85.6) and potential absolute risk reduction with statin drugs (OR, 6.7; 95% CI, 2.2-19.7), and had less decisional conflict (difference, -10.6; 95% CI, -15.4 to -5.9 on a 100-point scale) than did patients in the control group (n = 46). Of 33 patients in the intervention group taking statin drugs at 3 months, 2 reported missing 1 dose or more in the last week compared with 6 of 29 patients in the control group taking statin drugs (OR, 3.4; 95% CI, 1.5-7.5). CONCLUSIONS: A decision aid enhanced decision making about statin drugs and may have favorably affected drug adherence.