Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

Perioperative Acute Ischemic Stroke in Patients with Atrial Fibrillation.

OBJECTIVE: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures. METHODS: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis-Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision-Clinical Modification (ICD-10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA2 DS2 VASc to estimate periprocedural AIS risk. RESULTS: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42-1.76), renal failure (aOR = 1.14, 95% CI = 1.04-1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84-5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52-2.97), and higher CHA2 DS2 VASc scores (aOR 1.25 per point, 95% CI 1.22-1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA2 DS2 VASc (AUC = 0.60, 95% CI = 0.60 to 0.61). INTERPRETATION: In patients with AF, periprocedural AIS risk increases with the CHA2 DS2 VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321-329.

Radiographic predictors of aneurysmal etiology in patients with aneurysmal pattern subarachnoid hemorrhage.

OBJECTIVE: Spontaneous angiogram-negative nonperimesencephalic subarachnoid hemorrhage (an-NPSAH) can represent a diagnostic and management dilemma. The authors sought to determine radiographic predictors of aneurysmal etiology based on admission noncontrast head CT scans. METHODS: The authors performed a retrospective cohort study of prospectively collected data from consecutive patients who were admitted for spontaneous subarachnoid hemorrhage (SAH) with suspected aneurysmal etiology to an academic center from 2016 to 2021. They compared blood thickness in the basal cisterns and sylvian fissures and modified Graeb scores on admission head CT scans between the two groups and subsequently developed a predictive model to identify aneurysmal etiology. RESULTS: Of 259 included patients (mean age 56 years [SD 12.7 years]; 55% female), 209 had aneurysmal SAH (aSAH) and 50 had an-NPSAH. The median modified Graeb scores were similar for aSAH and an-NPSAH (6 [IQR 2-10] vs 3.5 [IQR 0-8.5], p = 0.33). The mean blood thickness was greater in the sylvian fissure (p = 0.010) and interhemispheric cisterns (p = 0.002), and there was a greater median degree of extension of blood in the sylvian fissures (p = 0.001) in aSAH than in an-NPSAH patients, but the mean blood thickness was less in the prepontine cistern (p = 0.014). The authors' scoring model was constructed based on differences in radiographic features. Receiver operating characteristic curve analysis showed acceptable accuracy in predicting aneurysmal etiology (area under the curve 0.71, 95% CI 0.62-0.79). CONCLUSIONS: There are differences in radiographic features on admission head CT between an-NPSAH and aSAH patients. The authors' proposed risk stratification model may be considered for further development and use in clinical practice in the future.

A quantitative model to differentiate nonaneurysmal perimesencephalic subarachnoid hemorrhage from aneurysmal etiology.

OBJECTIVE: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (pmSAH) is considered to have a lower-risk pattern than other types of subarachnoid hemorrhage (SAH). However, a minority of patients with pmSAH may harbor a causative posterior circulation aneurysm. To exclude this possibility, many institutions pursue exhaustive imaging. In this study the authors aimed to develop a novel predictive model based on initial noncontrast head CT (NCHCT) features to differentiate pmSAH from aneurysmal causes. METHODS: The authors retrospectively reviewed patients admitted to an academic center for treatment of a suspected aneurysmal SAH (aSAH) during the period from 2016 to 2021. Patients with a final diagnosis of pmSAH or posterior circulation aSAH were included. Using NCHCT, the thickness (continuous variable) and location of blood in basal cisterns and sylvian fissures (categorical variables) were compared between groups. A scoring system was created using features that were significantly different between groups. Receiver operating characteristic curve analysis was used to measure the accuracy of this model in predicting aneurysmal etiology. A separate patient cohort was used for external validation of this model. RESULTS: Of 420 SAH cases, 48 patients with pmSAH and 37 with posterior circulation aSAH were identified. Blood thickness measurements in the crural and ambient cisterns and interhemispheric and sylvian fissures and degree of extension into the sylvian fissure were all significantly different between groups (all p < 0.001). The authors developed a 10-point scoring model to predict aneurysmal causes with high accuracy (area under the curve [AUC] 0.99; 95% CI 0.98-1.00; OR per point increase 10; 95% CI 2.18-46.4). External validation resulted in persistently high accuracy (AUC 0.97; 95% CI 0.92-1.00) of this model. CONCLUSIONS: A risk stratification score using initial blood clot burden may accurately differentiate between aneurysmal and nonaneurysmal pmSAH. Larger prospective studies are encouraged to further validate this quantitative tool.

Risk Factors for Opioid Utilization in Patients with Intracerebral Hemorrhage.

BACKGROUND: Headache is a common presenting symptom of intracerebral hemorrhage (ICH) and often necessitates treatment with opioid medications. However, opioid prescribing patterns in patients with ICH are not well described. We aimed to characterize the prevalence and risk factors for short and longer-term opioid use in patients with ICH. METHODS: We conducted a retrospective cohort study using data from a single-center registry of patients with nontraumatic ICH. This registry included data on demographics, ICH-related characteristics, and premorbid, inpatient, and postdischarge medications. After excluding patients who died or received end-of-life care, we used multivariable regression models adjusted for premorbid opioid use to determine demographic and ICH-related risk factors for inpatient and postdischarge opioid use. RESULTS: Of 468 patients with ICH in our cohort, 15% (n = 70) had premorbid opioid use, 53% (n = 248) received opioids during hospitalization, and 12% (n = 53) were prescribed opioids at discharge. The most commonly used opioids during hospitalization were fentanyl (38%), oxycodone (30%), morphine (26%), and hydromorphone (7%). Patients who received opioids during hospitalization were younger (univariate: median [interquartile range] 64 [53.5-74] vs. 76 [67-83] years, p < 0.001; multivariable: odds ratio [OR] 0.96 per year, 95% confidence interval [CI] 0.94-0.98) and had larger ICH volumes (univariate: median [interquartile range] 10.1 [2.1-28.6] vs. 2.7 [0.8-9.9] cm3, p < 0.001; multivariable: OR 1.05 per cm3, 95% CI 1.03-1.08) than those who did not receive opioids. All patients who had external ventricular drain placement and craniotomy/craniectomy received inpatient opioids. Additional risk factors for increased inpatient opioid use included infratentorial ICH location (OR 4.8, 95% CI 2.3-10.0), presence of intraventricular hemorrhage (OR 3.9, 95% CI 2.2-7.0), underlying vascular lesions (OR 3.0, 95% CI 1.1-8.1), and other secondary ICH etiologies (OR 7.5, 95% CI 1.7-32.8). Vascular lesions (OR 4.0, 95% CI 1.3-12.5), malignancy (OR 5.0, 95% CI 1.5-16.4), vasculopathy (OR 10.0, 95% CI 1.8-54.2), and other secondary etiologies (OR 7.2, 95% CI 1.8-29.9) were also risk factors for increased opioid prescriptions at discharge. Among patients who received opioid prescriptions at discharge, 43% (23 of 53) continued to refill their prescriptions at 3 months post discharge. CONCLUSIONS: Inpatient opioid use in patients with ICH is common, with some risk factors that may be mechanistically connected to primary headache pathophysiology. However, the lower frequency of opioid prescriptions at discharge suggests that inpatient opioid use does not necessarily lead to a high rate of long-term opioid dependence in patients with ICH.

Psychological Aspects of the Israeli-Palestinian Conflict: A Systematic Review.

Despite ongoing local and international peace efforts, the Jews, Arabs, and other residents of Israel and the Palestinian territories (i.e., the West Bank and Gaza) have endured decades of political, social, and physical upheaval, with periodic eruptions of violence. It has been theorized that the psychological impact of the Israeli-Palestinian conflict extends beyond the bounds of psychiatric disorders such as posttraumatic stress disorder (PTSD). Exposure to the ongoing conflict may lead to changes in the way Israelis and Palestinians think, feel, and act; while these changes may not meet the thresholds of PTSD or depression, they nonetheless could have a strong public health impact. It is unclear whether existing studies have found associations between exposure to the conflict and nonclinical psychological outcomes. We conducted a systematic review to synthesize the empirical research on the Israeli-Palestinian conflict and its psychological consequences. As a whole, the body of literature we reviewed suggests that exposure to regional political conflict and violence may have detrimental effects on psychological well-being and that these effects likely extend beyond the psychiatric disorders and symptoms most commonly studied. We found evidence that exposure to the conflict informs not only the way Israelis and Palestinians think, feel, and act but also their attitudes toward different religious and ethnic groups and their degree of support for peace or war. We also found that Palestinians may be at particularly high risk of experiencing psychological distress as a result of the conflict, though more research is needed to determine the extent to which this is due to socioeconomic stress. Our review suggests the need for more studies on the nonclinical psychological aspects of the Israeli-Palestinian conflict as well as for longitudinal studies on the impact of the conflict on both Israelis and Palestinians.

Abdominal Visceral Fat Area and Chronic Pouchitis after Ileal Pouch-Anal Anastomosis.

Chronic pouchitis (CP) after ileal pouch-anal anastomosis is a significant clinical problem. Adipose tissues produce antiinflammatory cytokines and chemokines. We evaluated the association between abdominal visceral fat area (VFA) and CP. Patients with a preoperative CT evaluation were included. The diagnosis of CP was confirmed in all cases by endoscopy with afferent ileal limb intubation. Patients were allocated into groups of high VFA and low VFA. The study cohort of 52 patients had a median body mass index of 22 (range, 14-32). Indications for surgery were medically refractory disease in 46 (88%) patients and cancer/dysplasia in six (12%) patients. Median VFA was 27.1 (range, 1-144). Six (12%) patients developed CP. Low VFA patients were significantly younger (29 vs 45 years; P < 0.0001), had lower body mass index (20.4 vs 24.7; P < 0.0001), had surgery more commonly for medically refractory disease than for cancer or dysplasia (100 vs 77%; P = 0.02), and had a higher incidence of CP than high VFA patients (23 vs 0%; P = 0.02). Multiple linear regression analysis demonstrated that only low VFA was associated with CP (P = 0.009). An association is present between VFA and CP after ileal pouch-anal anastomosis, implicating adipocytes in the pathogenesis of inflammatory bowel disease.

Assessing the Quality and Value of Psychological Health Care in Civilian Health Plans: Lessons and Implications for the Military Health System.

The Military Health System (MHS) strives to provide high-quality care and improve outcomes for individuals with psychological health conditions. Over the last decade, the MHS has provided care to a growing number of individuals with psychological health conditions, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, little is known about the extent to which the MHS delivers care that is consistent with evidence-based clinical practice guidelines or if it is achieving positive outcomes for its service members. To better understand these issues, the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE) asked the RAND Corporation to describe civilian health plansâ; approaches to systematically measuring the quality of psychological health care delivered by providers in their networks. This work was part of a larger effort by RAND to develop a framework and identify a set of measures for monitoring the quality of care provided by the MHS for psychological health conditions.

Measuring the Quality of Care for Psychological Health Conditions in the Military Health System: Candidate Quality Measures for Posttraumatic Stress Disorder and Major Depressive Disorder.

In recent years, the number of U.S. service members treated for psychological health conditions has increased substantially. In particular, at least two psychological health conditions-posttraumatic stress disorder (PTSD) and major depressive disorder (MDD)-have become more common, with prevalence estimates up to 20 percent for PTSD and 37 percent for MDD. Delivering quality care to service members with these conditions is a high-priority goal for the military health system (MHS). Meeting this goal requires understanding the extent to which the care the MHS provides is consistent with evidence-based clinical practice guidelines and its own standards for quality. To better understand these issues, RAND Corporation researchers developed a framework to identify and classify a set of measures for monitoring the quality of care provided by the MHS for PTSD and MDD. The goal of this project was to identify, develop, and describe a set of candidate quality measures to assess care for PTSD and MDD. To accomplish this goal, the authors performed two tasks: (1) developed a conceptual framework for assessing the quality of care for psychological health conditions and (2) identified a candidate set of measures for monitoring, assessing, and improving the quality of care for PTSD and MDD. This article describes their research approach and the candidate measure sets for PTSD and MDD that they identified. The current task did not include implementation planning but provides the foundation for future RAND work to pilot a subset of these measures.

Succinylacetone as primary marker to detect tyrosinemia type I in newborns and its measurement by newborn screening programs.

Tyrosinemia type I (TYR I) is caused by autosomal recessive fumarylacetoacetate hydrolase deficiency and is characterized by development of severe liver disease in infancy and neurologic crises. If left untreated, most patients die of liver failure in the first years of life. Intervention with medication is effective when initiated during the first month of life. This improvement in the treatment of TYR I patients influenced the decision to include TYR I in the US Secretary of the Department of Health and Human Services' (HHS) Recommended Uniform Screening Panel. However, while tyrosine is routinely measured in newborn screening (NBS) by tandem mass spectrometry (MS/MS), elevated tyrosine levels are not specific to TYR I. To improve the specificity of NBS for TYR I, several assays were developed to measure succinylacetone (SUAC) in dried blood spots (DBS). SUAC is a pathognomonic marker of TYR I, and its detection by NBS MS/MS is possible. This review of the current status of NBS for TYR I in the US is the result of discussions at the HHS Secretary's (Discretionary) Advisory Committee on Heritable Disorders in Newborns and Children about the inconsistent implementation of effective NBS for TYR I in the US. We sought to understand the different TYR I screening practices in US NBS programs. Results indicate that 50 out of 51 NBS programs in the US screen for TYR I, and a successful SUAC performance evaluation scheme is available from the Centers for Disease Control and Prevention. Programmatic and methodological barriers were identified that prevent widespread adoption of SUAC measurements in NBS laboratories. However, since SUAC detection is currently the best approach to NBS for TYR I, a further delay of the addition of SUAC measurement into NBS procedures is discouraged. SUAC measurement should improve both the false positive and false negative rate in NBS for TYR I thereby yielding the desired benefits for affected patients at no expense to the overall population served.

Measuring Success in Health Care Value-Based Purchasing Programs: Findings from an Environmental Scan, Literature Review, and Expert Panel Discussions.

Value-based purchasing (VBP) refers to a broad set of performance-based payment strategies that link financial incentives to health care providers' performance on a set of defined measures in an effort to achieve better value. The U.S. Department of Health and Human Services is advancing the implementation of VBP across an array of health care settings in the Medicare program in response to requirements in the 2010 Patient Protection and Affordable Care Act, and policymakers are grappling with many decisions about how best to design and implement VBP programs so that they are successful in achieving stated goals. This article summarizes the current state of knowledge about VBP based on a review of the published literature, a review of publicly available documentation from VBP programs, and discussions with an expert panel composed of VBP program sponsors, health care providers and health systems, and academic researchers with VBP evaluation expertise. Three types of VBP models were the focus of the review: (1) pay-for-performance programs, (2) accountable care organizations, and (3) bundled payment programs. The authors report on VBP program goals and what constitutes success; the evidence on the impact of these programs; factors that characterize high- and low-performing providers in VBP programs; the measures, incentive structures, and benchmarks used by VBP programs; evidence on spillover effects and unintended consequences; and gaps in the knowledge base.

Technical challenges of a term delivery in a separated ischiopagus twin.

BACKGROUND: Conjoined twins occur in one in 100,000 live births. Successful term pregnancy in a separated conjoined twin is rare. CASE: We present a 27-year-old woman, gravida 2 para 0, former ischiopagus conjoined twin with successful separation at 12 days of life. We report a successful term gestation delivered by cesarean without complications. CONCLUSION: Term pregnancy is possible in a previous conjoined twin patient having undergone surgical separation. We recommend a multidisciplinary approach with close evaluation of maternal anatomy to achieve a successful pregnancy outcome while minimizing the risk of complications.

Prevalence of CGG expansions of the FMR1 gene in a US population-based sample.

The primary goal of this study was to calculate the prevalence of the premutation of the FMR1 gene and of the "gray zone" using a population-based sample of older adults in Wisconsin (n = 6,747 samples screened). Compared with past research, prevalence was relatively high (1 in 151 females and 1 in 468 males for the premutation and 1 in 35 females and 1 in 42 males for the gray zone as defined by 45-54 CGG repeats). A secondary study goal was to describe characteristics of individuals found to have the premutation (n = 30, 7 males and 23 females). We found that premutation carriers had a significantly higher rate of divorce than controls, as well as higher rates of symptoms that might be indicative of fragile X-associated tremor ataxia syndrome (FXTAS; numbness, dizziness/faintness) and fragile X primary ovarian insufficiency (FXPOI; age at last menstrual period). Although not statistically significant, premutation carriers were twice as likely to have a child with disability.

Hernia uterine inguinale: an uncommon cause of pelvic pain in the adult female patient.

Hernia uterine inguinale is a rare condition often presenting within the first few years of life as an asymptomatic palpable mass in the inguinal/groin area. This type of hernia contains uterine tissue and may contain oviducts, ovaries, and rarely the bladder. We report a case of a woman with a history of pelvic pain, found to have a rudimentary uterine horn herniating through the internal inguinal ring. A 24-year-old woman presented with noncyclic pelvic pain and irregular menses. Imaging revealed a solid 6- × 2-cm mass posterolateral to the ascending colon at the level of the pelvic brim in addition to absent right kidney and suspected unicornuate uterus. Laparoscopy with excision of the pelvic mass and appendectomy was performed. Surgical findings revealed a right rudimentary uterine horn herniating through the internal inguinal ring, attached to an elongated ovary/and an oviduct tightly tethered to the pelvic side wall. The result of pathologic study was consistent with rudimentary uterine horn, ovary with multiple cortical cysts, normal oviduct, and normal appendix. Hernia uterine inguinale is a rare condition and an even more uncommon cause of pelvic pain, instead presenting as an asymptomatic palpable groin mass early in life. This has been reported most commonly in the literature as both persistent müllerian duct syndrome and male pseudohermaphroditism. It is most often seen in a phenotypically normal male infant having both testes and uterine tissue present. Few cases have been documented to occur in the female sex, the adult patient, or as a cause of pelvic pain. Abdominal and pelvic imaging is useful in the diagnosis of this condition because it may aid in identifying patients with coexisting mullerian malformations. This subset may be at higher risk for hernia uterine inguinale, and, if presenting with complaints of pain or inguinal mass, it should likewise be considered in the differential diagnosis.

Prevalence, nature, and correlates of sleep problems among children with fragile X syndrome based on a large scale parent survey.

STUDY OBJECTIVES: This study reports on current child sleep difficulties reported by parents of children with Fragile X syndrome (FXS). We address prevalence and type of sleep problems (e.g., difficulty falling asleep, frequent awakenings); type and effectiveness of medical and behavioral treatments (e.g., medication, surgery, environmental changes); and explore specific child and family characteristics (e.g., child age, child gender, co-occurring conditions) as possible predictors of child sleep difficulties. DESIGN/PARTICIPANTS: This study is part of a larger survey addressing needs of families with children with FXS. This article focuses on the families who responded to the survey sleep questions, had one or more children with the full mutation FXS, and who reside in the United States. The mean age for male and female children in this group was 15 years and 16 years respectively (N=1295). RESULTS: Parents reported that 32% of the children with FXS currently experience sleep difficulties; 84% of those children are reported to have > or =2 current sleep problems. Problems falling asleep and frequent night awakenings were the most frequently reported difficulties; 47% of males and 40% of females received > or =1 medication to help with sleep. Children with more problematic health or behavioral characteristics had a higher likelihood of having current sleep problems. CONCLUSIONS: Our survey provides the most representative sample to date of sleep problems in children with FXS or any other neurodevelopmental disability. This large scale survey establishes a foundation for the prevalence of sleep disorders in children with FXS.

Modulation of the sympathetic response to acute hypoxia by the caudal ventrolateral medulla in rats.

Hypoxia elevates splanchnic sympathetic nerve activity (SNA) with differential effects during inspiration and expiration by unresolved central mechanisms. We examined the hypothesis that cardiovascular-related neurones in the caudal ventrolateral medulla (CVLM) contribute to the complex sympathetic response to hypoxia. In chloralose-anaesthetized, ventilated, vagotomized rats, acute hypoxia (10% O2, 60 s) evoked an increase in SNA (103 +/- 12%) that was characterized by a decrease in activity during early inspiration followed by a prominent rise during expiration. Some recorded baro-activated CVLM neurones (n = 13) were activated by hypoxia, and most of these neurones displayed peak activity during inspiration that was enhanced during hypoxia. In contrast, other baro-activated CVLM neurones were inhibited during hypoxia (n = 6), and most of these neurones showed peak activity during expiration prior to the onset of hypoxia. Microinjection of the glutamate antagonist kynurenate into the CVLM eliminated the respiratory-related fluctuations in SNA during hypoxia and exaggerated the magnitude of the sympathetic response. In contrast, microinjection of a GABA(A) antagonist (bicuculline or gabazine) into the CVLM dramatically attenuated the sympathetic response to hypoxia. These data suggest the response to hypoxia in baro-activated CVLM neurones is related to their basal pattern of respiratory-related activity, and changes in the activity of these neurones is consistent with a contribution to the respiratory-related sympathetic responses to hypoxia. Furthermore, both glutamate and GABA in the CVLM contribute to the complex sympathetic response to acute hypoxia.

Glutamatergic inputs to the CVLM independent of the NTS promote tonic inhibition of sympathetic vasomotor tone in rats.

GABAergic neurons in the caudal ventrolateral medulla (CVLM) are driven by baroreceptor inputs relayed via the nucleus tractus solitarius (NTS), and they inhibit neurons in rostral ventrolateral medulla to reduce sympathetic nerve activity (SNA) and arterial pressure (AP). After arterial baroreceptor denervation or lesions of the NTS, inhibition of the CVLM continues to increase AP, suggesting additional inputs also tonically activate the CVLM. This study examined whether the NTS contributes to baroreceptor-independent drive to the CVLM and whether glutamate promotes baroreceptor- and NTS-independent activation of the CVLM to tonically reduce SNA. In addition, we evaluated whether altering central respiratory drive, a baroreceptor-independent regulator of CVLM neurons, influences glutamatergic inputs to the CVLM. Splanchnic SNA and AP were measured in chloralose-anesthetized, ventilated, paralyzed rats. The infusion of nitroprusside decreased AP below threshold for baroreceptor afferent firing (<50 mmHg) and increased SNA to 209+/-22% (P<0.05), but the subsequent inhibition of the NTS by microinjection of the GABA(A) agonist muscimol did not further increase SNA. In contrast, after inhibition of the NTS, blockade of glutamatergic inputs to CVLM by microinjection of kynurenate increased SNA (274+/-54%; P<0.05; n=7). In vagotomized rats with baroreceptors unloaded, inhibition of glutamatergic inputs to CVLM evoked a larger rise in SNA when central respiratory drive was increased (219+/-16% vs. 271+/-17%; n=5; P<0.05). These data suggest that baroreceptor inputs provide the major drive for the NTS-mediated excitation of the CVLM. Furthermore, glutamate tonically activates the CVLM to reduce SNA independent of the NTS, and this excitatory input appears to be affected by the strength of central respiratory drive.

Impairment of sympathetic baroreceptor reflexes in obese Zucker rats.

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension. At 13 wk, adult OZRs had an elevated baseline mean AP compared with LZRs (137 +/- 3 vs. 123 +/- 5 mmHg, P < 0.05) under urethane anesthesia. Phenylephrine-induced increases in AP evoked smaller inhibitions of splanchnic sympathetic nerve activity (SNA) and HR in OZRs compared with LZRs. In addition, sympathoexcitatory responses to nitroprusside-induced hypotension were also blunted in OZRs. Sigmoid analysis revealed a decreased gain, a higher mean AP at the midpoint of the curve (AP(50)), and a reduced range of changes in SNA in OZRs. In contrast, at 7 wk of age, although juvenile OZRs weighed more than LZRs (313 +/- 13 vs. 204 +/- 4 g, P < 0.05), mean AP was comparable in both groups (122 +/- 5 vs. 121 +/- 4 mmHg, not significant). In these rats, rapid changes in AP evoked comparable changes in SNA and HR in OZRs and LZRs. Sigmoid analysis revealed that, although the gain of the reflex was blunted in OZRs (P < 0.05), the mean AP(50) and range of changes in SNA were comparable in OZRs and LZRs. Together, these data indicate that in adult OZRs, sympathetic responses to acute changes in AP are smaller than those observed in adult LZRs and that impairment of baroreceptor reflexes in OZR is not limited to the regulation of HR but extends to sympathetic vasomotor control. In addition, most of these deficits in baroreflex control of SNA develop in adulthood long after the onset of obesity and when other deficits in cardiovascular regulation are present.