Background and Purpose— Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation (AF). We sought to identify those most likely to have subclinical AF. Methods— We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Results— Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile range, 142–1973) among those who subsequently had AF detected versus 45 (interquartile range, 14–250) in those without AF ( P <0.001). APB count was the only significant predictor of AF detection by 30-day ECG ( P <0.0001), and at 90 days ( P =0.0017) and 2 years ( P =0.0027). Compared with the 16% overall 90-day AF detection rate, the probability of AF increased from <9% among patients with <100 APBs/24 h to 9% to 24% in those with 100 to 499 APBs/24 h, 25% to 37% with 500 to 999 APBs/24 h, 37% to 40% with 1000 to 1499 APBs/24 h, and 40% beyond 1500 APBs/24 h. Conclusions— Among older cryptogenic stroke or transient ischemic attack patients, the number of APBs on a routine 24-hour Holter ECG was a strong dose-dependent independent predictor of prevalent subclinical AF. Those with frequent APBs have a high probability of AF and represent ideal candidates for prolonged ECG monitoring for AF detection. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00846924.

If the intraluminal pressure of the brain is decreased for 24 hr, the brain and neuroepithelium volumes are both reduced in half. The current study measured the intraluminal pressure throughout the period of rapid brain growth using a servo-null micropressure monitoring system. From 613 measurements made on 55 embryos, we show that the intraluminal pressure over this time period is appropriately described by a linear model with correlation coefficient of 0.752. To assess whether sustained hyperpressure would increase mitosis, elevated intraluminal pressure was induced in 10 embryos for 1-hr duration via a gravity-fed drip. The mitotic density and index of the mesencephalon were measured for the 10 embryos. Those embryos, in which the colchicine solution was added to the intraluminal cerebrospinal fluid creating a sustained hyperpressure, exhibited at least a 2.5-fold increase in both the mitotic density and index compared with control embryos. Based on the small sample size, we cautiously conclude that sustained hyper-intraluminal pressure does stimulate mitosis.

The brain expands in the early chick embryo from pressure generated by accumulation of cerebrospinal fluid (CSF) in a closed neural tube. The sealing of the neural tube occurs as the result of occlusion of the spinal neurocoel rostral to and before closure of the posterior neuropore. We have previously demonstrated the dependence of normal brain expansion upon intraluminal pressure.We had yet to demonstrate, however, that brain expansion actually depends upon natural occlusion of the spinal neurocoel. To demonstrate such dependence, we experimentally occluded the spinal neurocoels of embryos 5 hr younger than stage 11 embryos (in which occlusion of the neurocoel occurs naturally). The stage 10 chick embryos were cultured ex ovo and critically staged, and their spinal neurocoels were occluded using microcautery. All embryos were photographed immediately and at 5, 12, and 24 hr after cautery. Serial sections were made of selected embryos, in which the areas of both the brain and the head were measured. Wilcoxon-Mann-Whitney rank-sum nonparametric tests, Hodges-Lehmann estimators, bootstrapping techniques, and resampling randomization tests were used to determine whether the increases in the brain and head areas for the experimental embryos were significantly different from those of the control embryos during three distinct intervals of expansion: 0 -5, 5-12, and 0 -12 hr. From 0 to 5 hr, the brains of the precociously occluded embryos expanded significantly more than the brains of the nonoccluded controls. From 5 to 12 hr, the brains of the embryos with naturally occluded neurocoels grew significantly larger than the brains of the embryos with precociously occluded neurocoels. At 12 hr, there appeared to be no difference in brain size for these two groups. We conclude that the data support the hypothesis that brain expansion is directly dependent upon occlusion of the spinal neurocoel. Anat Rec 268: 147-159, 2002.

This report focuses on growth of the brain of the early human embryo, Carnegie stages 12-23. Areas of median sections from 50 to 58 embryos were measured to determine the best mathematical model to describe growth of the three primary brain vesicles and to determine the change in the ratio of tissue to cavity areas (T/C). An exponential model best describes growth of the brain and head during this time period. The head expands 248-fold compared with a 171-fold growth of the brain. The whole brain, forebrain, and midbrain all exhibit larger cavities than tissue initially followed by a reversal of such at a critical time (stages 21-24). The presumptive cerebellar tissue which was twice the cavity initially grows to become more than six times the cavity. Boxplots of the T/C ratios for the head and brain plus its components reveal that initially the tissue is less than the cavity (10-20% and 40-60%, respectively) but eventually becomes larger Key words: growth parameters; brain expansion; mathematical models; CSF; cerebrospinal fluid pressure The brain and spinal cord or the central nervous system (CNS) first becomes apparent between the fourth and eighth weeks of development in the human (Desmond and O'Rahilly, 1981;O'Rahilly and Muller, 2006). Human embryology texts feature the elaborate changes in morphology that occur in the CNS during this time period but are remiss in conveying the tremendous growth of the embryonic CNS during these 4 weeks (Moore and Persaud, 2008a,b;Sadler, 2006). In fact, only one article exists in the literature to this day that documents such growth. This was a study reported more than 25 years ago by Desmond and O'Rahilly in which they measured the major axes of the three embryo brain vesicles. In that study, they compared the growth of the brain during the embryonic period, 4 to 8 weeks, with the fetal period, 8 weeks to birth. The study was limited to measuring one-dimensional lengths of the three major axes of the three embryo brain vesicles, namely, the bi-temporal (ear to ear) measurement, the frontal-occipital (forehead to back-of-head) measurement, and the dorsal-ventral (top-of-head to base) measurement. These findings, based on using one-dimensional axes, showed that the rates of growth of all three embryonic brain vesicles was much greater than the corresponding vesicles of the fetal period (Desmond and O'Rahilly, 1981).Interestingly, many of the current texts of human embryology draw attention to some of the more prominent abnormalities of the central nervous system such as hydrocephalus, spina bifida, and the Chiari type II malformation (Moore and Persaud, 2008a,b;Sadler, 2006). These same texts make no mention of the growth of the CNS and how mechanisms of growth might well play a role in these malformations.

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