Clinical characteristics and brain MRI findings in myeloproliferative neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV) and essential thrombocythemia (ET) have an increased risk of ischemic stroke. However, little is known about brain morphological changes and the cerebral vasculature in MPNs. The aim of the present study is to clarify the prevalence rates of brain infarcts (BIs) on magnetic resonance imaging (MRI) and to assess the detailed clinical and MRI characteristics in those patients. METHODS: We prospectively enrolled patients with MPNs who underwent brain MRI between September 2017 and June 2019. BI patterns were characterized by the numbers and locations of BIs on MRI. RESULTS: A total of 101 patients were included in the present study. BIs were observed in 23 patients (23%). Multiple logistic regression analysis showed that age > 60 years (odds ratio (OR) 7.34, 95% confidence interval (CI) 1.08-49.7, p = .041) and history of thrombosis (OR 40.6, 95% CI 7.97-207, p < .0001) were independently associated with BIs, but not the JAK2V617F mutation. Of the 23 patients with BIs, eight patients (35%) had multiple territorial infarcts, and large vessel involvement was identified in five patients (22%). Two patients had thrombus formation in large vessels. CONCLUSIONS: Among patients with MPNs who underwent MRI, BIs were observed in 23% of patients followed up in our center. Older age and thrombosis history were independently associated with BIs. Some patients with MPNs may present with distinctive MRI findings including multiple territorial infarcts and thrombus formation in large vessels.

Early Cognitive Assessment Following Acute Stroke: Feasibility and Comparison between Mini-Mental State Examination and Montreal Cognitive Assessment.

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

Low Free Triiodothyronine Predicts 3-Month Poor Outcome After Acute Stroke.

BACKGROUND AND PURPOSE: The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS: We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS: Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS: Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke.

About 30% of wake-up stroke patients may be candidate for the tPA therapy using Negative-FLAIR as a "tissue clock".

BACKGROUND AND PURPOSE: Recent studies using magnetic resonance imaging (MRI) have reported that wake-up stroke (WUS) patients may be able to be treated using tissue-plasminogen activator (tPA) when showing no ischemia on fluid-attenuated inversion recovery (Negative-FLAIR). We investigated the frequency of WUS and calculated what percentage of WUS patients with Negative-FLAIR meets most of the conventional tPA criteria. We did not include a time parameter in this study. METHODS: Consecutive patients with acute stroke affecting the anterior circulation who presented within 12h of onset were enrolled. All patients were examined using diffusion-weighted imaging (DWI) and FLAIR. As large infarctions are excluded from tPA therapy, an Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) of ≤3 was used as the upper limit for exclusion. RESULTS: A total of 816 consecutive patients were included in the study and were separated into two groups; 163 (20%) WUS patients as the WUS group, and 653 (80%) non-WUS patients as the non-WUS group. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7 (interquartile range, 3-17) in the WUS group and 8 (3-16) in the non-WUS group (p=0.313). MRI study revealed Negative-FLAIR in 67 (41%) of 163 patients in the WUS group. Of the 67 patients with Negative-FLAIR, 19 patients were excluded from tPA therapy. Therefore, 48 (29%) of the 163 wake-up stroke patients met the tPA criteria. CONCLUSIONS: About 30% of WUS patients may be candidates for tPA therapy based upon Negative-FLAIR findings.

The susceptibility vessel sign at the proximal M1: a strong predictor for poor outcome after intravenous thrombolysis.

BACKGROUND: Half of acute stroke patients have poor outcomes at 3 months even when treated with intravenous thrombolysis using tissue-plasminogen activator (t-PA) therapy. The aim of the present study was to evaluate the impact of the susceptibility vessel sign (SVS) on magnetic resonance imaging (MRI) T2* at the proximal portion of the middle cerebral artery (M1 proximal SVS) on clinical outcome in anterior circulation stroke patients treated with t-PA. METHODS: The presence of the M1 proximal SVS was assessed before t-PA therapy. Good outcome and poor outcome at 3 months were defined as a modified Rankin Scale score of 0 to 2 and 4 to 6, respectively. The predictive values of the M1 proximal SVS for a good and poor outcome were calculated. RESULTS: 161 patients (median age [interquartile], 76 [67-83] years; male, 91 [57%]) were enrolled. At 3 months after stroke, 68 (42%) patients achieved a good outcome, and 75 (47%) had a poor outcome. The M1 proximal SVS was found in 17 (11%) patients, of whom none (0%) achieved a good outcome, and 16 (94%) had a poor outcome. The sensitivity and positive predictive value of the M1 proximal SVS for good outcome were very low (0.000 and 0.000, respectively). Furthermore, the specificity and positive predictive value of the M1 proximal SVS for poor outcome were very high (0.988 and 0.941, respectively). CONCLUSION: The M1 proximal SVS appears to be a strong predictor for poor outcome after t-PA therapy.

Overexpression of inducible cyclic AMP early repressor inhibits transactivation of genes and cell proliferation in pancreatic beta cells.

Transcriptional control mediated by the cyclic AMP-responsive element (CRE) represents an important mechanism of gene regulation. To test our hypothesis that increased inducible cyclic AMP early repressor (ICER) Igamma inhibits function of CRE-binding proteins and thus disrupts CRE-mediated transcription in pancreatic beta cells, we generated transgenic mice with beta-cell-directed expression of ICER Igamma, a powerful repressor that is greatly increased in diabetes. Three transgenic lines clearly show that increased ICER Igamma expression in beta cells results in early severe diabetes. From birth islets were severely disorganized with a significantly increased proportion of alpha cells throughout the islet. Diabetes results from the combined effects of impaired insulin expression and a decreased number of beta cells. The decrease in beta cells appears to result from impaired proliferation rather than from increased apoptosis after birth. Cyclin A gene expression is impaired by the strong inhibition of ICER; the suppression of cyclin A results in a substantially decreased proliferation of beta cells in the postnatal period. These results suggest that CRE and CRE-binding factors have an important role in pancreatic beta-cell physiology not only directly by regulation of gene trans-activation but also indirectly by regulation of beta-cell mass.