Delayed postoperative hyponatremia after transsphenoidal surgery: prevalence and associated factors.

OBJECT: Transient delayed postoperative hyponatremia (DPH) after transsphenoidal surgery (TSS) is common and can have potentially devastating consequences. However, the true prevalence of transient symptomatic and asymptomatic DPH has not been studied in a large patient cohort with close and accurate follow-up. METHODS: A retrospective analysis of a single-institution prospective database was conducted; all patients undergoing TSS for lesions involving the pituitary gland were followed up in a multidisciplinary neuroendocrine clinic, and demographic, imaging, and clinical data were prospectively collected. Patients were examined preoperatively and followed up postoperatively in a standardized fashion, and their postoperative sodium levels were measured at Weeks 1 and 2 postoperatively. Levels of hyponatremia were rated as mild (serum sodium concentration 130-134 mEq/L), moderate (125-129 mEq/L), or severe (< 125 mEq/L). Routine clinical questionnaires were administered at all postoperative office visits. Postoperative hyponatremia was analyzed for correlations with demographic and clinical features and with immediate postoperative physiological characteristics. RESULTS: Over a 4-year interval, 373 procedures were performed in 339 patients who underwent TSS for sellar and parasellar lesions involving the pituitary gland. The mean (± SD) age of patients was 48 ± 18 years; 61.3% of the patients were female and 46.1% were obese (defined as a body mass index [BMI] ≥ 30). The overall prevalence of DPH within the first 30 days postoperatively was 15.0%; 7.2% of the patients had mild, 3.8% moderate, and 3.8% severe hyponatremia. The incidence of symptomatic hyponatremia requiring hospitalization was 6.4%. The Fisher exact test detected a statistically significant association of DPH with female sex (p = 0.027) and a low BMI (p = 0.001). Spearman rank correlation detected a statistically significant association between BMI and nadir serum sodium concentration (r = 0.158, p = 0.002) and an inverse association for age (r = -0.113, p = 0.031). Multivariate analyses revealed a positive correlation between postoperative hyponatremia and a low BMI and a trend toward association with age; there were no associations between other preoperative demographic or perioperative risk factors, including immediate postoperative alterations in serum sodium concentration. Patients were treated with standardized protocols for hyponatremia, and DPH was not associated with permanent morbidity or mortality. CONCLUSIONS: Delayed postoperative hyponatremia was a common result of TSS; a low BMI was the only clear predictor of which patients will develop DPH. Alterations in immediate postoperative sodium levels did not predict DPH. Therefore, an appropriate index of suspicion and close postoperative monitoring of serum sodium concentration should be maintained for these patients, and an appropriate treatment should be undertaken when hyponatremia is identified.

Transcatheter left atrial appendage occlusion.

Occlusion of the left atrial appendage (LAA) may reduce the risk of stroke in patients with atrial fibrillation (AF). Trials comparing LAA occlusion to warfarin anticoagulation in patients with nonvalvular AF showed a reduction in hemorrhagic stroke, although an increase in safety events due to procedural complications. Long-term follow-up suggests possible superiority of LAA occlusion due to fewer strokes and bleeding events. The superior dosing and safety profiles of the novel oral anticoagulants raise the accepted threshold for safety and efficacy of LAA occlusion procedures, and underscore the need for randomized studies comparing LAA occlusion with these newer anticoagulants.

Aspirin's effect on platelet inhibition in migraineurs.

OBJECTIVE: To assess the effect of aspirin on platelet reactivity in migraineurs. BACKGROUND: Migraineurs, particularly women with aura and high monthly migraine frequency, are at risk for ischemic stroke and myocardial infarction (MI). High on-aspirin platelet reactivity (HAPR), or aspirin resistance, has been reported in females and patients with coronary artery disease, and is associated with adverse outcomes. METHODS: Using a single group, pretest/posttest design, 50 migraineurs without prior history of stroke or MI were prospectively treated for 14 to 21 consecutive days with 325 mg generic enteric-coated aspirin, after undergoing a 14-day aspirin washout. Platelet reactivity was measured after aspirin washout and following aspirin treatment. Subjects were screened for HAPR using the VerifyNow™ Aspirin Assay (Accumetrics, San Diego, CA, USA). HAPR was defined as ≥ 460 Aspirin Reaction Units (ARU; primary endpoint). RESULTS: Fifty subjects, 44 (88%) female, aged (mean ± standard deviation) 43 ± 12 years were enrolled. Twelve (24%; 95% CI 12-36%) subjects, all female, had HAPR and were classified as aspirin resistant. Subjects with HAPR had lower baseline hemoglobin levels than those without HAPR (P = .03). Baseline hemoglobin was significantly correlated with final ARU (r = -0.39, P = .005). CONCLUSIONS: Findings of this exploratory study suggest that migraineurs have a higher prevalence of HAPR than healthy volunteers or patients with coronary artery disease taking aspirin 325 mg. The clinical implications of HAPR in migraine warrant further exploration due to the risk of stroke and MI and the potential need for antiplatelet therapy in this population.

Stroke prevention in atrial fibrillation: atrial appendage closure.

The left atrial appendage (LAA) is the primary nonvalvular cause of cardioembolic stroke in patients with atrial fibrillation (AF). Warfarin and direct thrombin inhibitors such as dabigatran are presumed to prevent formation of LAA thrombus, and are first-line treatments to prevent ischemic stroke in AF. However, these medications carry many contraindications such as hemorrhage, and can interact with many drugs and supplements. Epicardial and endovascular techniques for occlusion of LAA are being explored, whether to mitigate the need for anticoagulation in patients at risk of bleeding or as a first-line therapy to reduce the risk of thromboembolic stroke. The purposes of this article are to 1) review the LAA structure and its potential contribution to ischemic stroke; 2) discuss the results of surgical and endovascular trials of LAA occlusion on risk of stroke and adverse events in AF patients; and 3) present early data on devices in development.

Migraine and patent foramen ovale: state of the science.

Migraine is a prominent cause of recurrent pain, affecting 12% of the population. In several case series, approximately 50% of migraineurs with aura were found to have patent foramen ovale (PFO). The pathophysiological mechanism is speculated to be passage of microemboli and vasoactive chemicals through the PFO, thereby evading pulmonary filtration and triggering migraine symptoms. This article presents the results of retrospective and prospective research studies documenting the effects of PFO closure on migraine symptoms and presents emerging theories on possible pathologic mechanisms that may partially explain the increased risk of ischemic stroke in the migraine population. Finally, evidence-based recommendations are presented for health care providers for managing patients who have migraine and PFO.

Diagnosis of secondary source of right-to-left shunt with balloon occlusion of patent foramen ovale and power M-mode transcranial Doppler.

OBJECTIVES: We sought to assess the prevalence of secondary right-to-left circulatory shunt (RLS) in patients undergoing transcatheter closure of patent foramen ovale (PFO) as detected by power M-mode transcranial Doppler (TCD) and intracardiac echocardiography. BACKGROUND: Prevalence of residual RLS in late follow-up after PFO closure may be as high as 34%. Other cardiac and noncardiac sources of RLS may coexist and obscure PFO closure evaluation. METHODS: Eighty-eight patients who underwent transcatheter PFO closure to prevent recurrent paradoxical cerebral embolism between June 2005 and December 2006 were evaluated for a secondary source of RLS. Before device deployment, a sizing balloon was inflated in the PFO tunnel and agitated saline contrast was injected into the inferior vena cava. Clinically significant secondary RLS was defined as >10 embolic tracks on TCD at rest or immediately after calibrated (40 mm Hg), sustained (10 s) respiratory strain, with corresponding negative color-flow Doppler. Late residual RLS was evaluated in all patients with TCD and transthoracic echocardiography (mean: 192 days; 95% confidence interval [CI]: 161 to 223 days). RESULTS: The sample (n = 84) was 59% female, age 49 +/- 14 years. Seventeen patients (20%; 95% CI: 11.7 to 28.8) had secondary RLS during balloon occlusion. At late follow-up (n = 66), 13 of 14 (93%) patients with secondary RLS and 23 of 52 (44%) patients without secondary RLS had residual RLS (p = 0.002). CONCLUSIONS: This is the first report to systematically assess the prevalence of secondary RLS in patients undergoing PFO closure. Residual RLS detected by TCD may be due to secondary RLS, which may have implications for clinical outcomes.

Unilateral versus bilateral middle cerebral artery detection of right-to-left shunt by power M-mode transcranial doppler.

BACKGROUND AND PURPOSE: Comparison was performed between unilateral and bilateral power M-mode transcranial Doppler to detect right-to-left circulatory shunt (RLS). METHODS: Recorded Doppler data from 87 patients with confirmed RLS referred for transcatheter closure of patent foramen ovale were reanalyzed for embolic tracks (ET) counted from left and right temporal bone windows during bubble study. Unilateral counts were obtained by multiplying each side by 2; bilateral counts were obtained by summing left and right ET. Both unilateral and bilateral ET were converted to a 6-point logarithmic grade. Sex and age group subanalyses were performed. RESULTS: At rest, significantly more ET were detected with bilateral versus unilateral detection (P= .01), but not following Valsalva (P= .13). Unilateral and bilateral detection were equally able to detect large RLS (grades IV or V) following Valsalva (P= 1.00). For the group aged > or =55 years, the right-hand side yielded greater ET than the left-hand side (mean difference 9%+/- 37; 95% confidence interval -3 to 21%) at rest (P= .01), but not following Valsalva (mean difference 1%+/- 25; 95% confidence interval -7 to 9%, P= .10). CONCLUSIONS: Unilateral detection of ET by power M-mode transcranial Doppler is equivalent to bilateral detection to assess RLS.

Frequency of migraine headache relief following patent foramen ovale "closure" despite residual right-to-left shunt.

Retrospective studies have shown improvement in migraines after patent foramen ovale (PFO) closure. To date, no study has evaluated whether the completeness of closure affects headache status; therefore, the objective of this study was to evaluate the impact of residual right-to-left shunt (RLS) on migraine symptoms after transcatheter PFO closure in migraineurs with and without aura. This was a small-series, single-center, retrospective analysis of late follow-up data on 77 patients with presumed paradoxical embolism and migraine who underwent PFO closure for secondary stroke prevention. Power M-mode transcranial Doppler was used to assess RLS at baseline and 6 and 12 months after closure. A standardized migraine questionnaire was administered at baseline and 6, 12, and 24 months after closure. Fifty-five (71%) patients had migraine with aura. Final closure and migraine status were available for 67 patients; 23 (34%) had incomplete PFO closure, defined as 30 embolic tracks detected at final power M-mode transcranial Doppler examination (median 366 days, 95% confidence interval 332 to 474). Migraine relief (> or = 50% reduction in frequency) was independent of closure status (77% complete closure vs 83% incomplete closure, p = 0.76) at late follow-up (540 days, 95% confidence interval 537 to 711). Migraineurs with aura were 4.5 times more likely to experience migraine relief than migraineurs without aura. In conclusion, migraine relief may occur despite residual RLS after transcatheter PFO closure, which may suggest a reduction in RLS burden below a neuronal threshold that triggers migraine; however, this warrants further investigation. Migraine with aura may be an independent predictor of relief after PFO closure.

Migraineurs with patent foramen ovale have larger right-to-left shunt despite similar atrial septal characteristics.

The objective of the study was to assess differences in proportion of large right-to-left shunt (RLS) and atrial septal characteristics between migraineurs and non-migraineurs referred for transcatheter closure of patent foramen ovale (PF0). This retrospective study took place in a large metropolitan medical centre. The patients were migraineurs with aura (n=52), migraineurs without aura (n=19) and non-migraineurs (n=149). RLS was evaluated before closure using bilateral power m-mode transcranial Doppler at rest and after calibrated, sustained Valsalva manoeuvre, and graded with a validated 0-5 scale. Intracardiac echocardiography was used to assess atrial septal characteristics. Migraineurs had a higher proportion of large RLS (Grade IV or V) than nonmigraineurs at rest and after calibrated Valsalva (rest, p=0.04; Valsalva, p=0.01). Atrial septal characteristics were similar between groups. Migraine is associated with larger RLS at rest and strain; however migraine status does not predict PFO characteristics.

Outcomes after transcatheter closure of patent foramen ovale in patients with paradoxical embolism.

The purpose of the present study was to assess clinical outcomes and closure status after the transcatheter closure of patent foramen ovale. Two hundred thirty-seven consecutive patients (mean age 53 +/- 15 years; 48% men) who underwent patent foramen ovale closure for the prevention of recurrent stroke were evaluated. Primary end points were death, recurrent stroke, and residual right-to-left shunt (RLS). Closure status was monitored at 1, 6, 12, 24, 36, and 48 months after the index procedure by power M-mode transcranial Doppler and was defined by the number of embolic tracks detected after the release of a sustained, calibrated Valsalva maneuver. During a mean follow-up period of 568 +/- 364 days, the cumulative event rate for recurrent stroke (n = 8) was 3.4%, for an estimated event-free survival of 0.94 (SE 0.03). There was a significant difference in the estimated probability of recurrent stroke for patients grouped by age (< or =55 years 1.4% vs >55 years 6.6%, p = 0.03). There were 7 deaths (3.0%), 1 secondary to and 6 unrelated to recurrent strokes, and 3 surgical explantations (1.3%). Event-free survival, defined as freedom from death, stroke, or explantation, was 0.92 (SE 0.02). The magnitude of RLS was significantly less at late follow-up compared with baseline (grade 4.6 +/- 0.7 vs 1.8 +/- 1.6, p <0.001). Complete closure or minimal residual RLS (grade 0 to II) was achieved in 66% of patients. Device type (CardioSEAL or Amplatzer) did not affect the risk for adverse events or the presence of large residual RLS. In conclusion, transcatheter patent foramen ovale closure is associated with a low recurrent stroke rate in long-term follow-up.

Patent foramen ovale and cerebrovascular diseases.

Patent foramen ovale (PFO) has been linked to ischemic strokes of undetermined cause (cryptogenic strokes). PFO-a remnant of fetal circulation when the foramen ovale does not seal after birth-can permit microemboli to escape the pulmonary filter into the intracranial circulation, causing stroke. Coexistent atrial septal aneurysm, pelvic deep vein thrombosis and inherited clotting factor deficiencies could potentiate stroke risk in patients with PFO. Transcatheter PFO closure, a minimally invasive procedure, is one technique used to prevent recurrent cerebrovascular events. A connection between PFO and migraine headache has been conceptualized from retrospective evidence of reduced migraine frequency and severity after PFO closure; however, prospective randomized trials are needed to verify the efficacy of PFO closure on migraine prevention. In this review we discuss embryologic origins, diagnostic techniques and treatment options for prevention of paradoxical embolism thought to be related to PFO, and the relation of PFO to cryptogenic stroke and migraine.

Immune status of physically active women during lactation.

PURPOSE: The purpose of this study was to provide baseline data on immune status of exercising and sedentary exclusively lactating women. Dietary intake and body composition were also investigated to determine whether they related to immune function. METHODS: Healthy, exclusively breastfeeding women with a body mass index between 20 and 30 kg x m were studied at 3 months postpartum. Participants in the exercise group (EG; N = 27) exercised aerobically at least 30 min x d, 3x wk, and women in the sedentary group (SG; N = 23) exercised once a week or less during the previous 6 wk. Immune status while at rest was determined by measuring: 1) a complete blood cell count and differential leukocyte count; 2) percentages and absolute counts of peripheral blood T cells (CD3+), cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), B cells (CD19+), and natural killer cells (CD56+); 3) neutrophil bacterial killing and oxidative burst activity; and 4) in vitro mitogenic responsiveness of lymphocytes. Cardiorespiratory fitness, body composition, and dietary intake were also measured. RESULTS: Participants in the EG had a significantly higher level of mean predicted cardiorespiratory fitness than women in the SG (39.5 +/- 1.1 vs 32.5 +/- 1.0 mL O2 x min x kg; P < 0.05); however, there were no significant differences in body composition or dietary intake. There were no significant differences in any of the indicators of immune status between groups. In addition, there were no significant relationships between body composition or dietary intake and immune status. CONCLUSIONS: The results of this study suggest that women may exercise moderately during lactation and increase their fitness level without impairing their immune function.