Role of Advanced Hemodynamic Ultrasound Evaluation in the Differential Diagnosis of Middle Cerebral Artery Stenosis: Introducing Morphological Criteria.

OBJECTIVE: The aim of the work described here was to determine the possible impact of the new technique advanced hemodynamic ultrasound evaluation (AHUSE) in identification of severe intracranial stenosis. Transcranial Doppler (TCD) and transcranial color-coded Doppler (TCCD) provide reliable velocimetric data, the indirect analysis of which allows us to obtain information on the patency of vessels and assumed stenosis range. However, very tight stenoses (>95%) cannot be detected with velocimetric criteria because of spectrum drops and the absence of high velocities, so that the right curve of the Spencer equation cannot be solved. Likewise, high velocities are not detected when analyzing morphologically long stenosis. Furthermore, the current classifications based on velocimetric criteria do not provide any categorization on stenoses with multiple acceleration points (MAPs). METHODS: With this Technical Note we aim to introduce, in addition to velocimetric criteria, more morphological criteria based on TCCD with the algorithm of AHUSE to optimize the characterization of intracranial stenosis (IS). TCCD-AHUSE relies on intensity-based next-generation techniques and can be used to identify IS with MAPs and simultaneously perform a morphological assessment of the stenosis length. RESULTS: We introduce a new technical ultrasound (U) approach that we tested in a sample of four different types of stenoses combining velocimetric data and AHUSE using Esaote Microvascularization (MicroV) technique to the M1 tract of the middle cerebral artery (MCA). CONCLUSION: The authors believe that a multiparametric evaluation is more sensitive and supports the clinician by introducing the morphological concept, not just the velocimetric concept, to differentiate the IS pattern of MCA. The potential for developing a diagnostic/prognostic algorithm is discussed.

[Atrial tachycardia degenerating into atrial fibrillation during recurrence of ischemic stroke: prolonged ECG monitoring in appropriately selected patients with embolic stroke of undetermined source]. / Tachicardia atriale che degenera in fibrillazione atriale durante recidiva di ictus ischemico: utilità diagnostica del monitoraggio ECG prolungato in pazienti con ictus embolico ad eziologia indeterminata adeguatamente selezionati.

The search for silent atrial tachyarrhythmias remains one of the cornerstones in patients suffering from embolic stroke of undetermined source. We report the case of a 76-year-old female patient suffering from recurrence of ischemic stroke, adequately selected based on the presence of predictors of atrial fibrillation (AF), to perform prolonged ECG monitoring. This recording allowed to document long-lasting AF triggered by atrial tachycardia. It was also possible to demonstrate a direct correlation between AF and new cerebral stroke.

GABAA receptor and anti-titin antibody encephalitis in a patient with thymoma.

Autoimmune encephalitis (AE) associated to antibodies against GABA A R is a rare form of encephalitis. On the other hand, thymoma has been linked to antibodies against both muscular and neuronal epitopes, even if concurrent positivity for more than one antibody is exceptional, and their contribution to the clinical course and treatment decision is unclear. We report a case of a 73-year-old male with AE associated with thymoma secreting both anti-GABAaR and anti-titin antibodies. Clinical presentation included status epilepticus, behavioural changes and cognitive decline. While the status was stopped with lacosamide, AE treatment included first- and second-line immunomodulation, in addition to thymoma's removal. Nonetheless, the patient experienced a worsening in cognitive and behavioural status.

The domino effect of acephalgic spontaneous intracranial hypotension.

Spontaneous intracranial hypotension results from a spinal CSF leak and usually presents with orthostatic headache, although acephalgic presentations have anecdotally been reported. The underlying low CSF volume, rarely, leads to serious complications such as cerebral venous thrombosis and coma. We report a patient presenting with cerebral venous thrombosis secondary to acephalgic spontaneous intracranial hypotension. An epidural blood patch was performed; nonetheless, the patient intracracal condition deteriorated to coma and neuroimages showed a deep brain swelling with midbrain distortion, subsequently complicated by intracranial pontine hemorrhage.

Age-specific rate of undiagnosed diabetes and prediabetes in acute stroke.

AIMS: We investigated age-specific rates of undiagnosed diabetes and prediabetes among patients with acute stroke. METHODS: We used data from 2223 patients with acute stroke consecutively admitted to an Italian Stroke Unit (SU) between 2010 and 2015. Information from medical records and glycated hemoglobin (HbA1c) measured on admission was retrospectively used to screen for diabetes and prediabetes defined according to standard criteria. RESULTS: Overall rate of diabetes undiagnosed at admission and diabetes still undiagnosed at SU discharge were 9.7% and 6.7% but age-specific prevalence peaked up to 12.0% and 9.0% after age 80. At admission, the proportion of all undiagnosed diabetes on total diabetes cases was one out of every two cases before age 60 and three out of every four cases after age 80. In these same age intervals, one out of every three diabetes cases was still undiagnosed at SU discharge. Regardless of age, about three out of ten patients with acute stroke had prediabetes. Less than 2% of these patients had a prediabetes diagnosis before or after SU admission. CONCLUSIONS: In patients with acute stroke, diabetes is substantially underdiagnosed before age 60 and after age 80. Prediabetes is highly prevalent but mostly undiagnosed at all ages.

Homocysteinemia and early outcome of acute ischemic stroke in elderly patients.

OBJECTIVES: Plasma total homocysteine (tHcy) is a risk factor for ischemic stroke (IS) but its relationship with IS outcome is uncertain. Moreover, previous studies underrepresented older IS patients, although risk of both hyperhomocysteinemia and IS increases with age. We investigated whether, in elderly patients with acute IS, tHcy measured on admission to the Stroke Unit (SU) is an independent predictor of SU discharge outcomes. MATERIALS AND METHODS: Data are for 644 consecutive patients aged 80.3 ± 8.7 years, admitted to an Italian SU with diagnosis of acute IS. Plasma tHcy was measured on SU admission. Investigated outcomes included mortality during SU stay and poor functional status (modified Rankin Scale score ≥3) at SU discharge for survivors. The association of plasma tHcy with the study outcomes was assessed using Odds Ratios (OR) and their corresponding 95% confidence intervals (95%CI) from logistic regression models adjusted for demographics, pre-stroke features, IS severity, and laboratory data on SU admission (serum C-reactive protein, serum albumin, and renal function). RESULTS: Median plasma tHcy was 16.7 µmol/L (interquartile range, 13.0-23.3 µmol/L). Outcome incidence was 5.3% for mortality and 49.7% for poor functional status. Plasma tHcy was unrelated to mortality in both univariate and multivariable-adjusted analyses. Conversely, plasma tHcy was associated with poor functional status of survivors in univariate analyses (P = 0.014). Multivariable-adjusted analyses showed that, compared to normal homocysteinemia (tHcy <16 µmol/L), risk of being discharged with poor functional status significantly increased for moderate (tHcy ≥30 mol/L) but not mild (16.0-29.9 µmol/L) hyperhomocysteinemia. CONCLUSIONS: In elderly patients with acute IS, high admission plasma tHcy is unrelated to mortality during SU stay but is an independent predictor of poor functional status at SU discharge in survivors. The association, however, is limited to patients with moderate hyperhomocysteinemia.

Thyroid function tests and early outcomes of acute ischemic stroke in older euthyroid patients.

Blood thyroid function tests (TFT) are routinely used to screen for thyroid disorders in several clinical settings. TFT on hospital admission may also be useful prognostic predictors of acute IS: according to recent evidence, poststroke outcome is better in patients with lower thyroid function and worse in those with higher thyroid function. However, previous reports are few and mostly compared patients with thyroid disorders to euthyroid patients. Thyroid disorders are known risk factors for cerebrovascular disease. However, hyperthyroidism is related to cardioembolic IS whereas hypothyroidism is related to atherosclerotic risk factors. Therefore, findings from available studies of TFT might just reflect the worse prognosis of cardioembolic IS compared to other IS subtypes. Another limitation of previous studies is the lack of information for older persons, who represent three quarters of all IS patients. In this paper, we investigated whether serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) measured on Stroke Unit (SU) admission are associated with early outcomes of acute IS in 775 euthyroid patients aged ≥65 years (mean age 80.1±8.7 years). Two composite outcomes were investigated: poor functional outcome (death during SU stay or disability at SU discharge), and unfavorable discharge setting (death during SU stay, transfer from SU to other acute hospital unit or transfer from SU to long-term care-facilities as opposed to direct discharge home). Analyses were performed using logistic regression models. Curvilinear associations were tested including TFT as polynomial terms. Models were adjusted for demographics, prestroke, and IS-related confounders. We found that lower TSH had a complex curvilinear association with poor functional outcome and that the shape of the associations changed with age. At age 65, the curve was U-shaped: outcome risk decreased with increasing TSH, reached its minimum at TSH near 3.00mUI/L and then started to rise. Between ages 70 and 75, however, the shape of the curve straightened and, starting from age 80 took an inverted U-shape: outcome risk rose with increasing TSH, reached its maximum at TSH values that progressively shifted upward with increasing age (from 1.70mU/L at age 80 to about 2.20mUI/L at age 90), then started to decrease. A linear inverse association was found between FT3 and unfavorable discharge setting. Our study suggests that measurement of TFT on SU admission can provide independent prognostic information for early outcomes of acute IS in older euthyroid patients.

Molecular aspects of atherogenesis: new insights and unsolved questions.

The development of atherosclerotic disease results from the interaction between environment and genetic make up. A key factor in atherogenesis is the oxidative modification of lipids, which is involved in the recruitment of mononuclear leukocytes to the arterial intima--a process regulated by several groups of adhesion molecules and cytokines. Activated leukocytes, as well as endothelial mitochondria, can produce reactive oxygen species (ROS) that are associated with endothelial dysfunction, a cause of reduced nitric oxide (NO) bioactivity and further ROS production. Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are nuclear receptors significantly involved in the control of lipid metabolism, inflammation and insulin sensitivity. Also, an emerging role has been suggested for G protein coupled receptors and for the small Ras and Rho GTPases in the regulation of the expression of endothelial NO synthase (eNOS) and of tissue factor, which are involved in thrombus formation and modulation of vascular tone. Further, the interactions among eNOS, cholesterol, oxidated LDL and caveola membranes are probably involved in some molecular changes observed in vascular diseases. Despite the relevance of oxidative processes in atherogenesis, anti-oxidants have failed to significantly improve atherosclerosis (ATS) prevention, while statins have proved to be the most successful drugs.

Increased prevalence of coeliac disease in autoimmune thyroiditis is restricted to aged patients.

Patients with autoimmune thyroiditis (AT) have an increased prevalence of coeliac disease (CD), an immune-mediated enteropathy. It is unknown, however, whether prevalence of CD in AT is affected by age. Sera from 514 patients with AT aged <65 yr (46+/-12 yr), 223 patients with AT aged >or=65 yr (71+/-5 yr), 300 controls aged <65 yr (45+/-12 yr), and 300 controls aged >or=65 yr (71+/-6 yr) were tested for IgA anti-tissue transglutaminase (anti-tTG) and antiendomysial antibodies (EmA). If anti-tTG or EmA IgA were positive, jejunal biopsy was performed to confirm CD diagnosis. Prevalence of CD was significantly higher in patients with AT aged >or=65 yr (3.6%, P=0.024) than in patients with AT aged <65 yr (0.6%), controls aged <65 yr and controls aged >or=65 yr (both 0.3%). Prevalence of CD did not significantly differ across patients with AT aged <65 yr, controls aged <65 yr and controls aged >or=65 yr. In conclusion, prevalence of CD is increased in AT but the association is limited to patients aged 65 years or older. Serological screening including anti-tTG-IgA is recommended in these patients.

Homocysteine and cognitive function in healthy elderly community dwellers in Italy.

BACKGROUND: Elevated plasma total homocysteine (tHcy) concentrations are common in the elderly and have been suggested to be a risk factor for dementia. OBJECTIVE: In an elderly population, we examined the relation between plasma tHcy and scores on the Mini-Mental State Examination (MMSE), a commonly used screening measure of cognitive impairment in general practice. DESIGN: Fasting plasma tHcy concentrations were measured in 650 healthy, cognitively normal Italian community dwellers aged > or = 65 y (x +/- SD: 72.8 +/- 6.0 y). Socioeconomic status; serum folate, vitamin B-12, and creatinine; other potential dietary and lifestyle determinants of tHcy; and conventional vascular disease risk factors were also assessed. RESULTS: Subjects with MMSE scores of 26-28 had higher plasma tHcy concentrations (12.7 micromol/L; range: 12.2-13.2 micromol/L) than did those with scores > 28 (11.9 micromol/L; 11.4-12.3 micromol/L; P < 0.01). Subjects with scores of 24-25 had higher plasma tHcy concentrations (14.5 micro mol/L; 13.5-15.6 micromol/L) than did subjects with scores of 26-28 (P < 0.01) or > 28 (P < 0.001). The risk of hyperhomocysteinemia (plasma tHcy > 15 micromol/L) was higher in subjects with scores of 24-25 (odds ratio: 3.81; 95% CI: 1.9, 7.5) or 26-28 (odds ratio: 1.96; 95% CI: 1.3, 3.0) than in those with scores > 28. The results did not change after adjustment for conventional vascular risk factors and for age, medical, dietary, and lifestyle determinants of plasma tHcy. CONCLUSION: Elevated plasma tHcy has an independent, graded association with concurrent cognitive impairment as measured with the MMSE in healthy elderly community dwellers.