Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Gold Coast criteria expand clinical trial eligibility in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Consensus criteria to formalize the diagnosis of amyotrophic lateral sclerosis (ALS) and refine clinical trial populations have evolved. The recently proposed Gold Coast consensus criteria are intended to simplify use and increase sensitivity. We aimed to evaluate the potential impact of these criteria on clinical trial eligibility. METHODS: We performed a single-center, retrospective study of people diagnosed with ALS between 2016 and 2021 to determine the numbers of those meeting Gold Coast, revised El Escorial (rEEC) criteria, and Awaji criteria. We identified the proportion of those who would have been eligible for participation in three major ALS clinical trials if Gold Coast were used in place of rEEC definite/probable criteria. (rEEC D/P). RESULTS: Two hundred six people with ALS were included in our study. 48.5% met Gold Coast criteria but not rEEC D/P. Using the Gold Coast criteria would result in higher rates of clinical trial eligibility after other inclusion criteria were met: 95.2% vs 42.5% (P < .001) in a phase III study of riluzole; 100% vs 31.0% (P = .002) in a phase III study of edaravone; and 95.6% vs 45.3% (P < .001) in an ongoing phase III study of sodium phenylbutyrate and taurursodiol. The sensitivity of the Gold Coast criteria (96.1%; 95% confidence interval [CI], 92.2%-98.2%) was significantly higher than that of rEEC D/P (47.6%; 95% CI, 40.6%-54.6%; for difference, χ2  = 117.6; P < .001). DISCUSSION: Until robust biomarkers are available to diagnose ALS, consensus diagnostic criteria remain necessary. Gold Coast criteria would expand research and clinical trial eligibility and improve external validity of clinical trial results.

Twice Negative PCR in a Patient With Herpes Simplex Virus Type 1 (HSV-1) Encephalitis.

Untreated herpes simplex virus type 1 (HSV-1) encephalitis is associated with high mortality. Missed cases can have devastating consequences. Detection of HSV-1 in cerebrospinal fluid (CSF) with polymerase chain reaction (PCR) is reported to have high sensitivity and specificity and is considered the diagnostic gold standard for HSV-1 encephalitis. In this article, we report a case of autopsy-confirmed HSV-1 encephalitis where CSF PCR returned negative on 2 occasions. A 64-year-old man presented with fever, left-sided weakness, and altered level of consciousness. Magnetic resonance imaging demonstrated right mesial temporal lobe diffusion restriction and electroencephalography showed right lateralized periodic discharges. Lumbar puncture was performed on day 1 for which CSF PCR returned negative for HSV-1. Empiric antiviral and antibiotic treatments were continued due to high clinical suspicion of HSV-1 encephalitis. Repeat lumbar puncture on day 5 was unchanged and empiric treatments were discontinued. On day 13, he developed status epilepticus requiring intensive care unit admission. A third CSF sample returned positive for HSV-1. Acyclovir was restarted but he continued to clinically worsen and supportive care was withdrawn. Autopsy confirmed widespread HSV-1 meningoencephalitis. Negative CSF PCR should be interpreted with caution in cases where there is high clinical suspicion of HSV-1 encephalitis. Current guidelines suggest repeating CSF HSV-1 PCR within 3 to 7 days in suspicious cases while continuing empiric therapy. However, missed cases can occur even with repeated testing. Empiric treatment with acyclovir should be considered in cases with high clinical suspicion of HSV-1 encephalitis, while investigations for alternate treatable diagnoses are continued.

Hemorrhagic encephalopathy associated with COVID-19.

The mechanisms for neurological complications of COVID-19, the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are not yet well understood. We present a critically ill man with a COVID-19-associated hemorrhagic encephalopathy. SARS-CoV-2 RNA was not detected in cerebrospinal fluid (CSF) or blood. CSF analyses suggested dysregulation of pro-inflammatory cytokine pathways, particularly tumor necrosis factor-α and interleukin-6, consistent with a cytokine release syndrome. The patient gradually recovered with supportive care and neurological rehabilitation. Awareness of this clinical entity may facilitate the identification of patients with a potentially remediable cause of encephalopathy in COVID-19.

National trends in hospital admission, case fatality, and sex differences in atrial fibrillation-related strokes.

BACKGROUND AND AIM: Atrial fibrillation is associated with increased risk of ischemic stroke and its global prevalence is increasing. We aimed to describe the contemporary temporal trends in hospital admissions, case fatality rate, as well as sex differences in atrial fibrillation-related stroke in Canada. METHODS: We conducted a retrospective cohort study using Canadian national administrative data to identify admissions to hospital for stroke with comorbid atrial fibrillation between 1 April 2007 and 31 March 2016. We determined temporal trends in the crude and the age- and sex-standardized admission and case fatality rates. We also evaluated for any sex differences in these outcomes. RESULTS: There were 222,100 admissions to hospital for ischemic (n = 182,990) or hemorrhagic (n = 39,110) stroke. Comorbid atrial fibrillation was present in 20.2% of admissions for ischemic strokes and 10.1% for hemorrhagic strokes. Over the study period, the age-sex adjusted proportion of admissions with atrial fibrillation increased from 16.3% to 20.5% (p = 0.02) for ischemic stroke and was stable for hemorrhagic stroke. In-hospital case fatality rate decreased for ischemic stroke with and without comorbid atrial fibrillation. Women aged 65 years and older with ischemic stroke were more likely to have comorbid atrial fibrillation compared to men, while this association was reversed in younger women. There were no sex differences in the case fatality rate for people with atrial fibrillation-related ischemic stroke. CONCLUSION: Atrial fibrillation is present in an increasing proportion of people hospitalized in Canada with ischemic stroke and disproportionately affects older women. Renewed focus is needed on atrial fibrillation-related stroke prevention with particular attention to sex disparities.

Intrathecal Morphine Following Lumbar Fusion: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Despite the potential for faster postoperative recovery and the ease of direct intraoperative injection, intrathecal morphine is rarely provided in lumbar spine surgery. OBJECTIVE: To evaluate the safety and efficacy of intrathecal morphine following lumbar fusion. METHODS: We randomly assigned 150 patients undergoing elective instrumented lumbar fusion to receive a single intrathecal injection of morphine (0.2 mg) or placebo (normal saline) immediately prior to wound closure. The primary outcome was pain on the visual-analogue scale during the first 24 h after surgery. Secondary outcomes included respiratory depression, treatment-related side effects, postoperative opioid requirements, and length of hospital stay. An intention-to-treat, repeated-measures analysis was used to estimate outcomes according to treatment in the primary analysis. RESULTS: The baseline characteristics of the 2 groups were similar. Intrathecal morphine reduced pain both at rest (32% area under the curves [AUCs] difference, P < .01) and with movement (22% AUCs difference, P < .02) during the initial 24 h after surgery. The risk of respiratory depression was not increased by intrathecal morphine (hazard ratio, 0.86; 95% confidence interval, 0.44 to 1.68; P = .66). Although postoperative opioid requirements were reduced with intrathecal morphine (P < .03), lengths of hospital stay were similar (P = .32). Other than a trend towards increased intermittent catheterization among patients assigned to intrathecal morphine (P = .09), treatment-related side effects did not significantly differ. The early benefits of intrathecal morphine on postoperative pain were no longer apparent after 48 h. CONCLUSION: A single intrathecal injection of 0.2 mg of morphine safely reduces postoperative pain following lumbar fusion.

Oblique Intrathecal Injection in Lumbar Spine Surgery: A Technical Note.

OBJECTIVES: Intrathecal morphine (ITM) is an efficacious method of providing postoperative analgesia and reducing pain associated complications. Despite adoption in many surgical fields, ITM has yet to become a standard of care in lumbar spine surgery. Spine surgeons' reticence to make use of the technique may in part be attributed to concerns of precipitating a cerebrospinal fluid (CSF) leak. METHODS: Herein we describe a method for oblique intrathecal injection during lumbar spine surgery to minimize risk of CSF leak. The dural sac is penetrated obliquely at a 30° angle to offset dural and arachnoid puncture sites. Oblique injection in instances of limited dural exposure is made possible by introducing a 60° bend to a standard 30-gauge needle. RESULTS: The technique was applied for injection of ITM or placebo in 104 cases of lumbar surgery in the setting of a randomized controlled trial. Injection was not performed in two cases (2/104, 1.9%) following preinjection dural tear. In the remaining 102 cases no instances of postoperative CSF leakage attributable to oblique intrathecal injection occurred. Three cases (3/102, 2.9%) of transient CSF leakage were observed immediately following intrathecal injection with no associated sequelae or requirement for postsurgical intervention. In two cases, the observed leak was repaired by sealing with fibrin glue, whereas in a single case the leak was self-limited requiring no intervention. CONCLUSIONS: Oblique dural puncture was not associated with increased incidence of postoperative CSF leakage. This safe and reliable method of delivery of ITM should therefore be routinely considered in lumbar spine surgery.