Enhancing stroke risk prediction in patients with transient ischemic attack: insights from a prospective cohort study implementing fast-track care.

Background and aims: Fast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management. Methods: Prospective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD2 score was also calculated. Results: We enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% [95% CI 1.4-3.3%] at 90 days, 2.9% [95% CI 1.9-4.2%] at 12 months and 7.1% [95% CI 5.4-9.0%] at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 [95% CI 11.3-20.4] in the overall cohort and 6.8 [95% CI 4.6-13.5] in patients with baseline ABCD2 of 6 to 7. Conclusion: Our findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration.

Tacrolimus-associated neurotoxicity isolated to the brainstem: two illustrative cases and a systematic review of the literature.

INTRODUCTION: Tacrolimus-associated neurotoxicity (TAN) manifests with wide clinical spectrum, ranging from mild tremors to severe encephalopathy. The isolated involvement of the brainstem is a rarely documented presentation of TAN, and its clinical and diagnostic characteristics are unclear. METHODS: We report two cases of brainstem-isolated TAN (bi-TAN). Moreover, we performed a systematic review of the literature on bi-TAN and extracted data concerning demographics, clinical characteristics, radiological features, and management. The systematic literature search followed PRISMA guidelines and a pre-defined protocol. RESULTS: Eleven patients, including our two, were identified (mean age: 41.3 years, ± 18.8; five males, 45%). Speech disturbance was the most common clinical presentation (45%). The mean latency from Tacrolimus initiation to bi-TAN onset was 26 days (± 30.8). Tacrolimus serum level tested above the reference range in three patients (mean: 26.83 ± 5.48). Brain MRI showed T2-FLAIR hyperintensities; three showed restricted diffusion on ADC maps. Neurological symptoms resolved completely in seven patients (63%) after Tacrolimus withdrawal or dose reduction. CONCLUSIONS: Our findings suggest that bi-TAN could represent a brainstem variant of posterior reversible encephalopathy syndrome. Recognition of bi-TAN as a potential cause of isolated brainstem lesions is crucial to disentangle the diagnostic work-up and ensure prompt withdrawal or reduction of the offending agent.

CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study.

OBJECTIVE: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. METHODS: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. RESULTS: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. CONCLUSIONS: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.

Probability of Cardioembolic vs. Atherothrombotic Pathogenesis of Cryptogenic Strokes in Older Patients.

Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.

Predicting Failure to Recover Swallowing in Patients with Severe Post-stroke Dysphagia: The DIsPHAGIc Score.

In post-stroke dysphagia, early identification of patients at highest risk of failing swallowing recovery (SR) would be useful to decide which of them should undergo percutaneous endoscopic gastrostomy. The studies on this subject were numerous but generally based on small statistical samples. In this retrospective study, 1232 patients with ischemic or hemorrhagic stroke (73.7 ± 13.0 years, 51% men) were assessed: 593 non-dysphagic, 351 partially dysphagic and 288 totally dysphagic. Among the latter, 45.1% could not recover oral intake. A score to assess the risk of failing SR was obtained from the group with total dysphagia, and further 210 patients with total post-stroke dysphagia were utilized for validation. A regular progression of stroke severity markers, complications and mortality was observed from non-dysphagic, to partially dysphagic, up to totally dysphagic patients. Among the latter, seven variables were independently associated with failure of SR, and formed the "DIsPHAGIc score": cerebral lesion Diameter ≥ 6 cm (+ 1), left frontal Ischemia (- 1), Partial anterior circulation syndrome (- 1), Hypoxia (+ 1), Antiplatelet drug (+ 1), GCS verbal reaction < 4 (+ 1), Internal capsule ischemia (- 1). The area under the ROC curve was 0.79 (95% CI 0.74-0.85). For total scores ≥ 2 there was a high risk of failing SR, with specificity 76.9%, sensitivity 72.1% and accuracy 74.7%. The application of the DIsPHAGIc score to the validation sample provided almost identical results. The evolution of post-stroke dysphagia towards irreversibility can be predicted by a simple, reproducible and robust scoring system based on 7 variables commonly available during hospitalization.

Prognostic significance of diabetes and stress hyperglycemia in acute stroke patients.

BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.

Increased intracranial arterial tortuosity is associated with worse cardiovascular outcome in patients with Loeys-Dietz syndrome.

The aim of our study was to evaluate the association between intracranial arterial tortuosity and cardiovascular outcome in patients with Loeys-Dietz syndrome (LDS). We performed a retrospective analysis of all patients with genetically confirmed LDS who underwent at least one brain MRA at our institution (n = 32); demographic and clinical features were evaluated in relation to the tortuosity of intracranial arteries as measured by tortuosity index (TI), which was calculated using the formula: [(centerline length) / (straight-line length)-1] × 100. Receiver operating characteristic curve analysis for intracranial TI and the binary end point of aortic surgery showed vertebrobasilar TI (VBTI) to be the best classifier among the examined arterial segments (AUC = 0.822). Patients with higher VBTI showed a greater incidence of aortic surgery (p < 0.001) and underwent more surgical and endovascular procedures (p = 0.006), with a higher rate of operations (p = 0.002). Kaplan-Meier analysis showed a significantly longer surgery-free survival in patients with lower arterial tortuosity (p < 0.001). At multivariate analysis, higher VBTI was associated with an increased risk of surgery (p < 0.001), which was independent of gene mutation and patient age. Increased VBTI is a marker of adverse cardiovascular outcome in patients with LDS, which can be easily measured on brain MRA, and may be useful in the management of this heterogeneous patient population.

Frontal predominant encephalopathy with early paligraphia as a distinctive signature of CAR T-cell therapy-related neurotoxicity.

Chimeric antigen receptor (CAR) T-cell therapy is an emerging highly effective treatment for refractory haematological malignancies. Unfortunately, its therapeutic benefit may be hampered by treatment-related toxicities, including neurotoxicity. Early aggressive treatment is paramount to prevent neurological sequelae, yet it potentially interferes with the anti-cancer action of CAR T-cells. We describe four CAR T-cells infused patients who presented with reiterative writing behaviours, namely paligraphia, as an early manifestation of neurotoxicity, and eventually developed frontal predominant encephalopathy (one mild, three severe). Paligraphia may represent an early, specific, and easily detectable clinical finding of CAR T-cell therapy-related neurotoxicity, potentially informing its management.

Association of Left Ventricular Hypertrophy and Atrial Fibrillation with Hemorrhagic Evolution of Small Vessel Disease.

OBJECTIVES: Cerebral small vessel disease (SVD) is often associated with hypertension and may evolve towards intracerebral hemorrhage (ICH) or lacunar ischemic stroke. However, the factors favoring the evolution towards ICH or lacunar stroke are not well understood. MATERIALS AND METHODS: This retrospective study included 326 consecutive patients (71.1±13.2 years, 38% women): 143 with deep ICH and 183 with lacunar lesions (LL) <2 cm, which were visible in a deep location on brain CT scan. Among LL patients, 143 had a small-artery occlusion (SAO) stroke according to the TOAST classification. Clinical characteristics plus laboratory and neuroradiological variables of these patients had been prospectively collected and a subgroup underwent echocardiography. RESULTS: In multivariate analysis, ICH patients (97% hypertensive), compared to SAO patients (89% hypertensive), had greater left ventricular wall thickness (LVWT; OR 4.15, 95%CI 1.64-10.53, for those with LVWT ≥ 1.4 cm, 70% of whom were hemorrhagic) and lower prevalence of white matter lesions (OR 0.30, 95%CI 0.13-0.70), ever smokers (OR 0.39, 95%CI 0.18-0.82) and diabetics (OR 0.29, 95% CI 0.10-0.84). Moreover, ICH patients had a greater prevalence of atrial fibrillation than LL patients (OR 3.14, 95%CI 1.11-8.93), and so they were more often anticoagulated. CONCLUSIONS: Most SVD patients were hypertensive, but those evolving towards ICH were characterized by organ damage at the cardiac level (increase in LVWT and atrial fibrillation), while those evolving towards lacunar stroke were characterized by a higher prevalence of smokers and diabetics, and by organ damage at the cerebral level (white matter lesions).

Effect of body-part specificity and meaning in gesture imitation in left hemisphere stroke patients.

Previous studies showed that imitation of finger and hand/arm gestures could be differentially impaired after brain damage. However, so far, the interaction between gesture meaning and body part in imitation deficits has not been fully assessed. In the present study, we aimed at filling this gap by testing 36 unilateral left brain-damaged patients with and without apraxia (20 apraxics), and 29 healthy controls on an imitation task of either finger or hand/arm meaningful (MF) gestures and meaningless (ML) movements, using a large sample of stimuli and controlling for the composition of the experimental list. Left-brain damaged patients imitated ML finger worse than hand/arm movements, whereas they did not show the same difference in MF gesture imitation. In addition, apraxic patients imitated finger movements worse than hand/arm movements. Furthermore, apraxic patients' imitation performance was equally affected irrespective of the action meaning, whereas non-apraxic patients showed better imitation performance on MF gestures. Results suggest that MF gestures are processed as a whole, as imitation of these gestures relies on the stored motor programs in long-term memory, independently of the body part involved. In contrast, ML movements seem to be processed through direct visuo-motor transformations, with left-brain damage specifically disrupting imitation performance of the more cognitive demanding finger movements.

Venous thromboembolism prevention with low molecular weight heparin may reduce hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: Subcutaneous heparin at a prophylactic dose (SHPD) is a rather common treatment in ischemic stroke, but whether it confers an increased risk of hemorrhagic transformation of cerebral infarct (HT) and whether its reduction or discontinuation favors HT regression are presently poorly understood. METHODS: Two samples of ischemic stroke patients with a cerebral lesion diameter ≥ 3 cm on brain CT scan, admitted over 7 years to our stroke unit, were retrospectively examined: (1) patients treated or not treated with SHPD (enoxaparin 4000 U/day), with subsequent assessment of possible HT appearance (N = 267, mean age 75.9 ± 12.8 years) and (2) patients treated with SHPD, with HT and subsequent reduction/discontinuation or maintenance of the initial dose, and subsequent assessment of HT evolution (N = 116, mean age 75.7 ± 11.1 years). HT severity was quantified according to the ECASS study (HT score). RESULTS: In the first sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and other possible confounders, SHPD was inversely associated with HT appearance (hazard ratio 0.62, 95% CI 0.39-0.98, P = 0.04). In the second sample, after adjustment for age, sex, stroke severity, cerebral lesion diameter, and initial HT severity, SHPD reduction/discontinuation had an inverse effect on both HT score improvement (odds ratio 0.42, 95% CI 0.18-0.99, P = 0.049) and HT improvement according to neuroradiological reports (odds ratio 0.34, 95% CI 0.14-0.82, P = 0.015). CONCLUSIONS: This retrospective study suggests that SHPD may play a protective role in HT appearance and evolution, which requires verification by a randomized clinical trial.

Usefulness of the ACTEL Score to Predict Atrial Fibrillation in Patients with Cryptogenic Stroke.

INTRODUCTION: To assess the probability of undetected atrial fibrillation (AF) in patients with ischemic stroke, we previously compared patients who were first diagnosed with AF with patients with large or small artery disease and obtained the MrWALLETS 8-item scoring system. In the present study, we utilized cryptogenic strokes (CS) as the control group, as AF is normally sought among CS patients. METHODS: We retrospectively examined 191 ischemic stroke patients (72.5 ± 12.6 years), 68 with first diagnosed AF and 123 with CS, who had undergone 2 brain CT scans, echocardiography, carotid/vertebral ultrasound, continuous electrocardiogram monitoring and anamnestic/laboratory search for cardiovascular risk factors. RESULTS: In logistic regression, 5 variables were independently associated with AF, forming the "ACTEL" score: Age ≥75 years (OR 2.42, 95% CI 1.18-4.96, p = 0.02; +1 point); hyperCholesterolemia (OR 0.38, 95% CI 0.18-0.78, p = 0.009; -1 point); Tricuspid regurgitation ≥ mild-to-moderate (OR 4.99, 95% CI 1.63-15.27, p = 0.005; +1 point); left ventricular End-diastolic volume <65 mL (OR 7.43, 95% CI 2.44-22.6, p = 0.0004; +1 point); Left atrium ≥4 cm (OR 4.57, 95% CI 1.97-10.62, p = 0.0004; +1 point). The algebraic sum of these points may range from -1 to +4. For AF identification, the area under the receiver operating characteristic curve was 0.80 (95% CI 0.73-0.87). With a cutoff of ≥2, positive predictive value was 80.8%, specificity 92.7% and sensitivity 55.9%. CONCLUSIONS: The ACTEL score, a simplified and improved version of the MrWALLETS score, allows the identification of patients with first diagnosed AF, in the context of CSs, with a high positive predictive value.

Predicting hemorrhagic transformation and its timing from maximum cerebral lesion diameter in nonlacunar ischemic strokes.

OBJECTIVES: We performed this retrospective cohort study to establish which factors are mostly indicative of the appearance of hemorrhagic transformation (HT) and of its time course in a sample of nonlacunar ischemic strokes. MATERIALS AND METHODS: In 402 patients with nonlacunar ischemic stroke (75.0 ± 12.7 years, 192 male), clinical, laboratory, and neuroimaging variables obtained during the first 3 days of hospitalization were compared between patients with and without HT at computer tomography scan. RESULTS: HT was documented in 129 patients (32.1%), including 36 with parenchymal hematoma (PH), after a median time of 6 days (range 1-27). Many variables were univariately associated with HT, but only 5 of them were confirmed in Cox regression (Hazard Ratio, 95% Confidence Interval): maximum cerebral lesion diameter (CLD) in cm (1.12, 1.06-1.18; p = .0001), hemoglobin in g/dl (1.16, 1.06-1.27; p = .002), blood glucose in mmol/L (1.10, 1.03-1.18; p = .007), prior anticoagulant therapy (1.82, 1.10-3.03; p = .02), and edema with mass effect (1.72, 1.08-2.75; p = .02). Thus, the most significant predictor was CLD. The overall risk of HT was minimum for CLD < 2 cm (1.5%), intermediate for CLD ≥ 2 and < 5 cm (22%), and maximum for CLD ≥ 5 cm (58%). The residual probability of having HT decreased progressively over time, and a simple formula is proposed to predict, from CLD in cm, when the probability of HT falls below 10%. CONCLUSIONS: The main determinant of HT was CLD, a simple quantitative parameter that could prove useful, in particular, in deciding the timing of anticoagulation in cardioembolic stroke patients.

Predicting cerebral edema in ischemic stroke patients.

OBJECTIVES: To produce a scoring system for predicting the development of edema in ischemic stroke patients without edema on admission. METHODS: This retrospective study included 572 ischemic stroke patients (73.3 ± 13.0 years, 300 male) without signs of cerebral edema on the first CT scan, which was performed on admission. Another scan was normally performed 3 days later, and subsequently whenever needed. Edema was defined as cerebral hypodensity with compression of lateral ventricles. The main clinical, laboratory, and instrumental variables obtained during the first 24 h were related to the appearance of edema on the CT scans performed after the first one. RESULTS: Cerebral edema occurred in 158 patients (27.6%) after a median time of 4 days. The variables independently associated with edema development were (odds ratio, 95% CI) the following: (1) total anterior circulation syndrome (4.20, 2.55-6.93; P < 0.0001), (2) hyperdense appearance of middle cerebral artery (4.12, 2.03-8.36; P = 0.0001), (3) closed eyes (2.53, 1.39-4.60; P = 0.002), (4) vomiting (3.53, 1.45-8.60; P = 0.006), (5) lacunar cerebral syndrome (0.36, 0.17-0.77; P = 0.008); and (6) white matter lesions (0.53, 0.33-0.86; P = 0.01). Counting one positive point for the first four variables and one negative point for the last two variables, a scoring system (E-score) was built. Cerebral edema could be predicted when the score was ≥ 1 (positive predictive value 61.6%, specificity 85.3%, sensitivity 62.0%). The area under the receiver operating characteristic curve was 0.78. CONCLUSIONS: In ischemic stroke patients, six variables obtained during the first 24 h of hospitalization were predictive of subsequent cerebral edema development.

Successful treatment of bilateral endogenous Fusarium solani endophthalmitis in a patient with acute lymphocytic leukaemia.

Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

Brain Metastases from Biliary Tract Cancer: A Monocentric Retrospective Analysis of 450 Patients.

OBJECTIVE: Brain metastases (BMs) from biliary tract cancer (BTC) are extremely rare. The aim of our study was to report the incidence of BMs in patients with BTC. METHODS: We retrospectively analyzed a series of 450 patients with BTC. Presence of brain lesions was investigated only when symptoms were evident. Cumulative incidence, median overall survival (OS) from detection of BMs, median OS from cancer diagnosis, and median time from cancer diagnosis to detection of BMs were evaluated. RESULTS: In our series, 6 patients developed BMs with an incidence of about 1.4%. Median OS from detection of BMs and from cancer diagnosis was, respectively, 3.7 (0.9-17.8) and 23 (9.9-57.6) months. Median time between cancer diagnosis and detection of BMs was 13.6 (7.3-52.8) months. Moreover, we observed a significant association between BMs and bone metastases (particularly vertebral lesions). DISCUSSION: Despite the retrospective design, this is the first study evaluating the incidence of BMs among patients with BTC in Western countries. BMs from BTC remain atypical, although their incidence is probably a little higher than previously assumed. Patients with BMs had poor prognosis. Unpredictably, bone involvement occurred in 5 out of 6 patients.

Usefulness of the MrWALLETS Scoring System to Predict First Diagnosed Atrial Fibrillation in Patients With Ischemic Stroke.

Some cryptogenic strokes are caused by undetected paroxysmal atrial fibrillation (AF) and could benefit from oral anticoagulation. In this study, we searched for echocardiographic parameters associated with first diagnosed AF, to form a scoring system for the identification of patients with AF. We examined 571 patients with ischemic stroke (72.7 ± 13.5 years, 50.6% women), subdivided into 4 groups: documented cause without AF, first diagnosed AF, known paroxysmal AF, and permanent AF. All patients underwent transthoracic echocardiography, brain computed tomography scan, carotid/vertebral ultrasound, and continuous electrocardiographic monitoring. Eight factors independently characterized first diagnosed AF and formed the "MrWALLETS" score: mitral regurgitation, mild-to-moderate (+1), white matter lesions (-1), age ≥75 years (+1), left atrium ≥4 cm (+1), cerebral lesion diameter ≥4 cm (+1), left ventricular end-diastolic volume <65 ml (+1), tricuspid regurgitation ≥moderate (+1), carotid stenosis ≥50% (-1). In the patients with ≥3 points, positive predictive value was 80%, specificity 97.5%, and sensitivity 57.1%. In the patients with ≥2 points sensitivity rose to 85.7%, but positive predictive value was 47.1%. The area under the receiver-operating characteristic curve was 0.89 (95% CI 0.83 to 0.95). There were important differences among AF groups, which therefore could not be merged. In conclusion, 4 echocardiographic parameters, 3 additional instrumental parameters, and age allow the identification of stroke patients with first diagnosed AF with high positive predictive value.

Risk Factors for Lacunar Strokes with Visible Cerebral Lesions on Computed Tomography Scan.

BACKGROUND: The aim of this study was the detection of risk factors for lacunar strokes with visible lesions on computed tomography (CT) scan, considering in particular clinical characteristics, echocardiographic parameters, and carotid-femoral pulse wave velocity (PWV, a marker of large-artery stiffness). Lacunar strokes with very small or nonvisible lesions may have different risk factors. METHODS: We examined 106 patients (mean age 66.9 ± 12.3 years, 60 men), including 55 patients with clinically lacunar stroke associated with deep ischemic lesions of .3-1.5 cm on brain CT scan, and 51 control patients with cortical ischemic stroke, with lesions of 2.5-10.0 cm. RESULTS: In multiple logistic regression, with respect to cortical strokes, the following variables were independently associated with lacunar strokes: tricuspid regurgitation velocity (inverse relationship, odds ratio [OR] .13, 95% confidence interval [CI] .04-.43, P = .0007, cutoff at 228 cm/s), mean systolic blood pressure (SBP) (OR 3.98, 95% CI 2.78-7.79, P = .008, cutoff at 145 mmHg), ever-smoker status (OR 2.68, 95% CI 1.06-6.80, P = .04), and atrial fibrillation (inverse relationship, OR .11, 95% CI .01-1.00, P = .0496). In univariate analysis, the patients with lacunar stroke also had a lower prevalence of mitral regurgitation. There were no differences between the 2 groups in relation to diabetes, cholesterol, left ventricular mass and dimensions, and PWV. CONCLUSIONS: The patients with lacunar strokes with visible cerebral lesions on CT scan, compared with the patients with cortical infarct, had a lower tricuspid regurgitation velocity, a higher mean SBP, a greater prevalence of ever-smokers, and a lower prevalence of atrial fibrillation.

Hypertension and Other Determinants of White Matter Lesions in Stroke Patients.

Hypertension is the main risk factor for both white matter lesions (WMLs) and stroke, but many stroke patients do not have WMLs. To find specific determinants of WMLs, the authors assessed 321 ischemic and hemorrhagic stroke patients who had undergone echocardiography. The patients with WMLs (n=160) were more often hypertensive and had a higher systolic blood pressure than the patients without WMLs. However, in a multivariate analysis, only the following variables remained associated with WMLs: (1) age: odds ratio [OR], 1.08 per year (95% confidence interval [CI], 1.06-1.11); (2) left ventricular relative wall thickness (RWT) ≥0.52: OR, 2.78 (95% CI, 1.59-4.88); (3) lacunar strokes: OR, 4.15 (95% CI, 1.83-9.44); (4) hemorrhagic strokes: OR, 5.36 (95% CI, 1.57-18.39); and (5) female: OR, 1.91 (95% CI, 1.12-3.27). Thus, the main modifiable risk factor for WMLs was RWT, which proved to be an even stronger risk factor than hypertension. This suggests that RWT might be a useful target in the treatment of hypertension to counteract the appearance of WMLs.