Antipyretic Efficacy of Bromocriptine in Central Fever: an Exploratory Analysis.

BACKGROUND: 'Central' fevers are thought to result from disruption of hypothalamic thermoregulatory pathways following severe brain injuries. Bromocriptine, due to its central dopamine receptor agonism, has been hypothesized to have antipyretic effect in this setting. However, clinical evidence for this off-label use is limited to a few case reports. In this retrospective cohort study, we analyzed the effect of bromocriptine administration on body temperature in acute brain injury patients with suspected central fever. METHODS: We screened a cohort of adult patients that received bromocriptine in the neurologic-intensive care unit of a tertiary care hospital between January 2018 and December 2021. Indication of central fever was ascertained by review of clinical documentation. A generalized additive mixed model (GAMM) was used to model temperature as a function of time relative to bromocriptine initiation. We adjusted for potential confounding due to the following covariates: temperature recording method (invasive vs surface), concurrent antipyretic administration within 8 h, and surface cooling device use within 4 h of temperature measurement. Temperature-time function was modeled using a cubic spline with k = 10 knots. RESULTS: A total of 33 patients were included in the analysis (14 women; mean age: 50 y, standard deviation 14 y). Median dose of bromocriptine was 7.5 mg (range 2.5-40) for a median of 13 d (range 5-160). Age and sex did not impact the function of temperature over time. Predicted temperatures were significantly (p < 0.05) higher by 0.4 °C with invasive compared to surface recording methods, lower by 0.2 °C in the presence of cooling device use and lower by 0.1 °C with concurrent antipyretic use. On adjusted analysis with the GAMM, there was decline (p < 0.05) in temperature following bromocriptine initiation by - 0.3 °C at 24 h, - 0.5 °C at 48 h, and - 0.7 °C at 72 h. CONCLUSIONS: Bromocriptine use was associated with modest but statistically significant decline in temperature, with nadir at 72 h post initiation. The findings provide a data driven basis for prospective evaluation.

Hemoglobin concentration does not impact 3-month outcome following acute ischemic stroke.

BACKGROUND: There is uncertainty regarding the effect of anemia and red blood cell transfusion on functional outcome following acute ischemic stroke. We studied the relationship of hemoglobin parameters and red cell transfusion with post stroke functional outcome after adjustment for neurological severity and medical comorbidities. METHODS: Retrospective cohort study of 536 patients discharged with a diagnosis of ischemic stroke from a tertiary care hospital between January 2012 and April 2015. Hemoglobin level at hospital admission, lowest recorded value during hospitalization (nadir), delta hemoglobin (admission minus nadir), red cell transfusion during hospitalization were noted. Charlson Comorbidity Index (CCI) was computed as a summary measure of medical comorbidities. A multivariable logistic regression model was used to determine risk-adjusted odds of unfavorable outcome, defined as a modified Rankin Score of > 2. RESULTS: Anemia was present on hospital admission in 31% of patients. Forty five percent of patients had unfavorable outcome. In the univariable analysis increasing age, admission National Institutes of Health Stroke Scale (NIHSS), CCI, nadir hemoglobin, delta hemoglobin and blood transfusion were associated with unfavorable outcome. In the multivariable model, only increasing age, CCI and NIHSS remained associated with unfavorable outcome. No quadratic association was found on repeating the model to identify a possible U-shaped relationship of hemoglobin with outcome. CONCLUSIONS: Our findings contradict prior observational studies and highlight an area of clinical equipoise regarding the optimal management of anemia in patients hospitalized for ischemic stroke. This uncertainty could be addressed with appropriately designed clinical trials.

Quality of life and psychiatric co­morbidity in Indian migraine patients: a headache clinic sample.

BACKGROUND: There is a lack of data from India on the impact of migraine on health-related quality of life (HRQoL) and the extent of psychiatric co-morbidities in migraine. OBJECTIVE: The objectives of the study were to quantify the impairment in HRQoL in migraine patients compared to healthy controls, to compare the prevalence of clinically significant anxiety and depressive symptoms in these groups, and to identify patient and headache characteristics that may predict health-related quality of life. MATERIALS AND METHODS: We interviewed 71 consecutive newly diagnosed migraine patients seen in the headache clinic of a tertiary referral center between September and December 2008. Age- and sex-matched healthy subjects (n = 71) were used as controls. Short Form-36, Migraine Disability Assessment Score, and Hospital Anxiety and Depression Scale were administered. Predictors of HRQoL were identified using regression analysis. RESULTS: Migraineurs were significantly impaired in all subscales of the SF-36 compared to controls, with greatest impairments in role physical, general health, and role emotional subscales. Prevalence of clinically significant anxiety (48%) and depressive (41%) symptoms in patients was higher than in healthy controls. Female gender, headache-related disability, and severity of anxiety predicted worse Physical Component Summary scores, while severity of both anxiety and depressive symptoms predicted worse Mental Component Summary scores. CONCLUSION: HRQoL is significantly reduced in Indian migraine patients compared to healthy controls. Incidence of clinically significant anxiety and depressive symptoms is also much higher in these patients. These findings corroborate well with studies from other parts of the world and suggest that cultural differences do not significantly alter the subjective impact of migraine on quality of life.

Multiple coinfections and Guillain Barré syndrome following outdoor travel to the American Northeast.

A 66-year-old immunocompetent man with preceding travel through the Northeastern United States developed Guillain-Barré syndrome. A broad search for infections revealed intraerythrocytic parasites on blood smear and positive polymerase chain reaction for Babesia microti; elevated IgM/IgG serologies for Ehrlichia chaffeensis; elevated IgM/IgG serologies and qualitative polymerase chain reaction for Epstein-Barr virus; and fecal culture growth of Arcobacter butzleri. In this report, we discuss the known or suspected association of these infectious agents with Guillain-Barré syndrome. This case also highlights the importance, in the setting of endemic exposure, of screening for multiple coinfections that can be transmitted by the same arthropod vector.

Cryptococcal Meningoencephalitis During Convalescence From Severe COVID-19 Pneumonia.

Invasive cryptococcal infection in a previously immunocompetent patient complicating coronavirus disease 2019 (COVID-19) pneumonia has not been described before. In this report, a 76-year-old woman survived a bout of respiratory failure from severe COVID-19 pneumonia, during which she received remdesivir, convalescent plasma, corticosteroids, and tocilizumab. Soon after discharge, she developed acute encephalopathy and multifocal ischemic strokes. CSF and blood cultures were positive for Cryptococcus neoformans. Cryptococcal meningoencephalitis should be considered in the differential diagnosis of encephalopathy in a patient with COVID-19. Treatment with high-dose steroids and tocilizumab may be predisposing factors.

Serum Neuron-Specific Enolase Thresholds for Predicting Postcardiac Arrest Outcome: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: To determine thresholds of serum neuron-specific enolase (NSE) for prediction of poor outcome after cardiac arrest with >95% specificity using a unique method of multiple thresholds meta-analysis. METHODS: Data from a systematic review by the European Resuscitation Council (ERC 2014) were updated with literature searches from PubMed, Cochrane, and Scopus until August 2020. Search terms included the MeSH terms "heart arrest" and "biomarkers" and the text words "cardiac arrest," "neuron specific enolase," "coma" and "prognosis." Cohort studies with comatose cardiac arrest survivors aged >16 years undergoing targeted temperature management (TTM) and NSE levels within 96 hours of resuscitation were included. Poor outcome was defined as cerebral performance category 3-5 at hospital discharge or later. Studies without extractable contingency tables were excluded. A multiple thresholds meta-analysis model was used to generate summary receiver operating characteristic curves for various time points. NSE thresholds (and 95% prediction intervals) for >95% specificity were calculated. Evidence appraisal was performed using a method adapted from the American Academy of Neurology grading criteria. RESULTS: Data from 11 studies (n = 1,982) at 0-24 hours, 21 studies (n = 2,815) at 24-48 hours, and 13 studies (n = 2,557) at 48-72 hours was analyzed. Areas under the curve for prediction of poor outcomes were significantly larger at 24-48 hours and 48-72 hours compared to 0-24 hours (0.82 and 0.83 vs 0.64). Quality of evidence was very low for most studies because of the risk of incorporation bias-knowledge of NSE levels potentially influenced life support withdrawal decisions. To minimize falsely pessimistic predictions, NSE thresholds at the upper 95% limit of prediction intervals are reported. For prediction of poor outcome with specificity >95%, upper limits of the prediction interval for NSE were 70.4 ng/mL at 24-48 hours and 58.6 ng/mL at 48-72 hours. Sensitivity analyses excluding studies with inconsistent TTM use or different outcome criteria did not substantially alter the results. CONCLUSIONS: NSE thresholds for highly specific prediction of poor outcome are much higher than generally used. Future studies must minimize bias by masking treatment teams to the results of potential predictors and by prespecifying criteria for withdrawal of life support.

CE: Hypertensive Emergencies: A Review.

ABSTRACT: While acute blood pressure elevations are commonly seen in the ED, not all require emergency treatment. True hypertensive emergencies are characterized by a rapid elevation in blood pressure to a level above 180/120 mmHg and are associated with acute target organ damage, which requires immediate hospitalization for close hemodynamic monitoring and IV pharmacotherapy. Recognizing the clinical signs and symptoms of hypertensive emergency, which may vary widely depending on the target organ involved, is critical. High blood pressure levels that produce no signs or symptoms of target organ damage may be treated without hospitalization through an increase in or reestablishment of previously prescribed oral antihypertensive medication. However, all patients presenting with blood pressure this high should undergo evaluation to confirm or rule out impending target organ damage, which differentiates hypertensive emergency from other hypertensive crises and is vital in facilitating appropriate emergency treatment. Drug therapy for hypertensive emergency is influenced by end-organ involvement, pharmacokinetics, potential adverse drug effects, and patient comorbidities. Frequent nursing intervention and close monitoring are crucial to recuperation. Here, the authors define the spectrum of uncontrolled hypertension; discuss the importance of distinguishing hypertensive emergencies from hypertensive urgencies; and describe the pathophysiology, clinical manifestations, and management of hypertensive emergencies.

Perirhinal cortex lesions delay ejaculation in rats.

Afferents from the perirhinal cortex (PRh) form a major input to the hippocampal formation, which is known to be involved in sexual behavior in rodents. But there is a lacuna in literature regarding the role of the PRh in sexual behavior. Bilateral neurotoxic lesions of the PRh delayed the ejaculation latency and prolonged the mean inter-intromission interval significantly, suggesting a facilitatory role of the PRh in male rat sex behavior.

Delayed onset paraparesis complicating epidural steroid injection with underlying spinal dural arteriovenous fistula.

We report a case of a 48-year-old man with chronic back pain attributed to discogenic lumbar radiculopathy who underwent a fluoroscopy-guided L2-3 interlaminar epidural steroid injection. 4 h later, he developed acute paraparesis, sensory loss below T10 level and urinary retention. MRI of the thoracic spine revealed diffuse abnormal T2/FLAIR signal and extensive vascular flow voids. A spinal dural arteriovenous fistula was confirmed on spinal angiography. Embolization of the spinal dural arteriovenous fistula resulted in significant improvement of symptoms. We review previously reported cases and current understanding of the pathophysiology of this complication. All cases had symptom onset several hours after the procedure. There seems to be a trend toward better outcomes with earlier treatment.

The effect of systemic PTEN antagonist peptides on axon growth and functional recovery after spinal cord injury.

Knockout studies suggest that PTEN limits the regenerative capacities of CNS axons as a dominant antagonist of PI3 kinase, but the transgenic approach is not feasible for treating patients. Although application of bisperoxovanadium may block PTEN function, it is a general inhibitor of phosphotyrosine phosphatases and may target enzymes other than PTEN, causing side effects and preventing firm conclusions about PTEN inhibition on regulating neuronal growth. A pharmacological method to selectively suppress PTEN post-injury could be a valuable strategy for promoting CNS axon regeneration. We identified PTEN antagonist peptides (PAPs) by targeting PTEN critical functional domains and evaluated their efficacy for promoting axon growth. Four PAPs (PAP 1-4) bound to PTEN protein expressed in COS7 cells and blocked PTEN signaling in vivo. Subcutaneous administration of PAPs initiated two days after dorsal over-hemisection injury significantly stimulated growth of descending serotonergic fibers in the caudal spinal cord of adult mice. Systemic PAPs induce significant sprouting of corticospinal fibers in the rostral spinal cord and limited growth of corticospinal axons in the caudal spinal cord. More importantly, PAP treatment enhanced recovery of locomotor function in adult rodents with spinal cord injury. This study may facilitate development of effective therapeutic agents for CNS injuries.

Scar-mediated inhibition and CSPG receptors in the CNS.

Severed axons in adult mammals do not regenerate appreciably after central nervous system (CNS) injury due to developmentally determined reductions in neuron-intrinsic growth capacity and extracellular environment for axon elongation. Chondroitin sulfate proteoglycans (CSPGs), which are generated by reactive scar tissues, are particularly potent contributors to the growth-limiting environment in mature CNS. Thus, surmounting the strong inhibition by CSPG-rich scar is an important therapeutic goal for achieving functional recovery after CNS injuries. As of now, the main in vivo approach to overcoming inhibition by CSPGs is enzymatic digestion with locally applied chondroitinase ABC (ChABC), but several disadvantages may prevent using this bacterial enzyme as a therapeutic option for patients. A better understanding of the molecular mechanisms underlying CSPG action is needed in order to develop more effective therapies to overcome CSPG-mediated inhibition of axon regeneration and/or sprouting. Because of their large size and dense negative charges, CSPGs were thought to act by non-specifically hindering the binding of matrix molecules to their cell surface receptors through steric interactions. Although this may be true, recent studies indicate that two members of the leukocyte common antigen related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ (PTPσ) and LAR, are functional receptors that bind CSPGs with high affinity and mediate CSPG inhibitory effects. CSPGs also may act by binding to two receptors for myelin-associated growth inhibitors, Nogo receptors 1 and 3 (NgR1 and NgR3). If confirmed, it would suggest that CSPGs have multiple mechanisms by which they inhibit axon growth, making them especially potent and difficult therapeutic targets. Identification of CSPG receptors is not only important for understanding the scar-mediated growth suppression, but also for developing novel and selective therapies to promote axon sprouting and/or regeneration after CNS injuries, including spinal cord injury (SCI).

Association of exclusive smokeless tobacco consumption with hypertension in an adult male rural population of India.

INTRODUCTION: Tobacco consumption is a major source of mortality and morbidity in India . Prevalence of smokeless tobacco (ST) consumption in India is around 20%. Studies have shown increased prevalence of cardiovascular disease risk factors and an increased incidence of adverse cardiovascular events among the ST consumers. This is a cross-sectional study done to look into the association of exclusive smokeless tobacco consumption with hypertension, in an adult male rural population of north India. METHODS: All male residents of a village in north India above 15 years of age, who did not have any acute or chronic morbidity were included after taking an informed consent. Subjects were interviewed regarding their demographic profile, socioeconomic status and tobacco consuming habits. Current smokeless tobacco user was defined as one who has ever consumed tobacco orally in past 1 month. Blood pressure of the subjects was also recorded. Cut offs used for systolic and diastolic hypertension were 140 mm hg and 90 mm Hg respectively. RESULTS: 443 subjects were included in the study. Prevalence of exclusive ST users was 21% while 19.4% consumed both forms and 26.6% did not take any form of tobacco. Mean systolic and diastolic BP were significantly higher in exclusive ST users(systolic BP=139.2+17.4,diastolic BP = 86.8+11.5)as compared to the non users(systolic BP= 135.7+18.8 , diastolic BP= 82.6 +11.5; p value < 0.05). The prevalence of diastolic hypertension was significantly higher in exclusive ST users as compared to non users ( 40.9%, 22.9% ;p value = 0.01) . The OR for diastolic hypertension in male ST users was 2.3( 95% C.I. = 1.3-4.3). Prevalence of systolic hypertension was higher in exclusive ST users too though this was not statistically significant (43%,36.4%;p value = 0.39.). CONCLUSION: ST consumption is associated with increased prevalence of high BP in the adult male rural population.This is an indicator of increased predisposition to major adverse cardiac events later in their life time. Prevention of ST consumption could be an important intervention in preventing the ongoing upswing in prevalence of chronic heart disease.