Cognitive Testing During Mild Acute Ischemic Stroke Predicts Long-Term Return to Work.

OBJECTIVES: Many survivors of a mild ischemic stroke do not return to work or driving. Cognitive testing is commonly done to assess long-term cognitive impairment after stroke. Inpatient cognitive testing during the acute period of ischemic stroke may also be a predictor for workforce reengagement and functional outcome. MATERIALS AND METHODS: At our comprehensive stroke center, we prospectively enrolled previously working adults < 65 years old who were diagnosed with first-ever ischemic stroke, had a prestroke modified Rankin Scale (mRS) ≤ 1 and NIHSS ≤ 3. Testing performed within 1 week of stroke included the Montreal Cognitive Assessment (MOCA), Clock Drawing Test (CDT), Trail Making Tests A and B, Backward Digit Span Test, and Hospital Anxiety and Depression Scale (HADS). Other data obtained included age, gender, years of education, occupation, stroke location, stroke laterality, and presence of white matter disease on imaging. Outcome measures assessed at 3 months, 6 months, and 12 months post-stroke included return to work, return to driving, and mRS. In a logistic regression analysis, we performed both univariate and multivariate analyses. Multivariate analysis was completed on variables with p-value ≤ 0.05 in the univariate analysis. RESULTS: Of 39 total stroke patients enrolled and tested (median [IQR] age 55 [46-60] years; 77.5% male; 22.5% female), 36 completed 3-month follow up, of which 58% returned to work, 78% returned to driving, and 72% had mRS of 0-1. In multivariate analysis, a single point increase in the clock drawing task score increased the odds of return to work by 3.79 (95% CI, 1.10-14.14) and return to driving by 6.74 (95% CI, 1.22-37.23) at 3 months. MOCA and HADS were both associated with mRS ≤ 1. MOCA was associated with return to work at 6 months and CDT was associated with return to work at 12 months. CONCLUSION: Cognitive testing with CDT and MOCA in the acute period after ischemic stroke may predict common patient goals post stroke, including return to work, driving, and independence. These tools can potentially be used for prognosis and identifying those who may benefit from further interventions.

Participation and consultation engagement strategies have complementary roles: A case study of patient and public involvement in clinical practice guideline development.

BACKGROUND: Patient and public involvement (PPI) is recommended when developing high-quality clinical practice guidelines, but the effects of different PPI strategies are largely unstudied. OBJECTIVE: To assess the impact of participation and consultation strategies on guideline question development. DESIGN: Instrumental case study design. SETTING AND PARTICIPANTS: This study used a clinical practice guideline in development by the American Academy of Neurology. A patient, two caregivers and a dementia advocate participated in the guideline development group alongside clinicians. The guideline protocol was posted for public consultation for 30 days. INTERVENTIONS STUDIED: Participation (patient representatives on the guideline development group) and consultation (public comment, survey) PPI strategies. MAIN OUTCOME MEASURES: Public comment responses and guideline development group meeting transcripts were analysed descriptively. Transcript quotes were compared to the conceptual model of PPI in guideline development. The effects of participation and consultation strategies within the guideline case were compared. RESULTS: Participation strategies shaped discussions, set a patient-centred scope, highlighted personal aspects of disease, affected how professionals viewed PPI, identified issues overlooked by medical professionals, and contributed to selecting patient-relevant guideline populations and outcomes. Professionals responded to public comment more than patient representatives. Patient survey participants confirmed the priorities voiced by patient representatives on the guideline development group. Final guideline questions included populations and outcomes promoted by patient representatives despite negative feedback from professional public commenters. DISCUSSION AND CONCLUSIONS: Participation and consultation PPI strategies have different advantages. Congruence between strategies increases the strength of the patient voice. Guideline developers should prioritize using both strategies for successful PPI.

Clinical Characteristics of Stroke with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) potentially increases the risk of thromboembolism and stroke. Numerous case reports and retrospective cohort studies have been published with mixed characteristics of COVID-19 patients with stroke regarding age, comorbidities, treatment, and outcome. We aimed to depict the frequency and clinical characteristics of COVID-19 patients with stroke. METHODS: PubMed and EMBASE were searched on June 10, 2020, to investigate COVID-19 and stroke through retrospective cross-sectional studies, case series/reports according to PRISMA guidelines. Study-specific estimates were combined using one-group meta-analysis in a random-effects model. RESULTS: 10 retrospective cohort studies and 16 case series/reports were identified including 183 patients with COVID-19 and stroke. The frequency of detected stroke in hospitalized COVID-19 patients was 1.1% ([95% confidential interval (CI)]: [0.6-1.6], I2 = 62.9%). Mean age was 66.6 ([58.4-74.9], I2 = 95.1%), 65.6% was male (61/93 patients). Mean days from symptom onset of COVID-19 to stroke was 8.0 ([4.1-11.9], p< 0.001, I2 = 93.1%). D-dimer was 3.3 µg/mL ([1.7-4.9], I2 = 86.3%), and cryptogenic stroke was most common as etiology at 50.7% ([31.0-70.4] I2 = 64.1%, 39/71patients). Case fatality rate was 44.2% ([27.9-60.5], I2 = 66.7%, 40/100 patients). CONCLUSIONS: This systematic review assessed the frequency and clinical characteristics of stroke in COVID-19 patients. The frequency of detected stroke in hospitalized COVID-19 patients was 1.1% and associated with older age and stroke risk factors. Frequent cryptogenic stroke and elevated d-dimer level support increased risk of thromboembolism in COVID-19 associated with high mortality. Further study is needed to elucidate the pathophysiology and prognosis of stroke in COVID-19 to achieve most effective care for this population.

Patient Stakeholder Versus Physician Preferences Regarding Amyloid PET Testing.

BACKGROUND: Patient and caregiver perspectives on amyloid positron emission tomography (PET) use are largely unexplored, particularly as compared with clinician views. METHODS: We surveyed clinicians, patients, caregivers, and dementia advocates on topics relating to an evidence-based guideline on amyloid PET use. Topic importance was rated on a 9-point scale. Patient stakeholder and clinician views were compared using the Mann-Whitney U test. RESULTS: Patient representatives (n=107) rated all survey topics as equal to or more important than clinicians (n=114) except 1 item discussing potential harms of false-positive diagnoses. Differences between patient representative and clinician populations were greatest when comparing the competing values of false-positive and false-negative diagnoses and the value of testing asymptomatic individuals. CONCLUSIONS: Patients and caregivers emphasized the importance of having a dementia diagnosis and placed more value on testing and outcomes for asymptomatic populations than clinicians. This underscores the importance of research investigating the effect of amyloid PET results on asymptomatic individuals and the need for amyloid PET ordering and disclosure standards.

Practice Guideline Update Recommendations Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research.

OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition on minimally conscious state (MCS) and provide care recommendations for patients with prolonged disorders of consciousness (DoC). METHODS: Recommendations were based on systematic review evidence, related evidence, care principles, and inferences using a modified Delphi consensus process according to the AAN 2011 process manual, as amended. RECOMMENDATIONS: Clinicians should identify and treat confounding conditions, optimize arousal, and perform serial standardized assessments to improve diagnostic accuracy in adults and children with prolonged DoC (Level B). Clinicians should counsel families that for adults, MCS (vs vegetative state [VS]/ unresponsive wakefulness syndrome [UWS]) and traumatic (vs nontraumatic) etiology are associated with more favorable outcomes (Level B). When prognosis is poor, long-term care must be discussed (Level A), acknowledging that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults (Level B); no tests are shown to improve prognostic accuracy in children. Pain always should be assessed and treated (Level B) and evidence supporting treatment approaches discussed (Level B). Clinicians should prescribe amantadine (100-200 mg bid) for adults with traumatic VS/UWS or MCS (4-16 weeks post injury) to hasten functional recovery and reduce disability early in recovery (Level B). Family counseling concerning children should acknowledge that natural history of recovery, prognosis, and treatment are not established (Level B). Recent evidence indicates that the term chronic VS/UWS should replace permanent VS, with duration specified (Level B). Additional recommendations are included.

Comprehensive Systematic Review Update Summary: Disorders of Consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research.

OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days. METHODS: Articles were classified per the AAN evidence-based classification system. Evidence synthesis occurred through a modified Grading of Recommendations Assessment, Development and Evaluation process. Recommendations were based on evidence, related evidence, care principles, and inferences according to the AAN 2011 process manual, as amended. RESULTS: No diagnostic assessment procedure had moderate or strong evidence for use. It is possible that a positive EMG response to command, EEG reactivity to sensory stimuli, laser-evoked potentials, and the Perturbational Complexity Index can distinguish MCS from vegetative state/unresponsive wakefulness syndrome (VS/UWS). The natural history of recovery from prolonged VS/UWS is better in traumatic than nontraumatic cases. MCS is generally associated with a better prognosis than VS (conclusions of low to moderate confidence in adult populations), and traumatic injury is generally associated with a better prognosis than nontraumatic injury (conclusions of low to moderate confidence in adult and pediatric populations). Findings concerning other prognostic features are stratified by etiology of injury (traumatic vs nontraumatic) and diagnosis (VS/UWS vs MCS) with low to moderate degrees of confidence. Therapeutic evidence is sparse. Amantadine probably hastens functional recovery in patients with MCS or VS/UWS secondary to severe traumatic brain injury over 4 weeks of treatment. Recommendations are presented separately.

Framework for enhancing clinical practice guidelines through continuous patient engagement.

BACKGROUND: Patient engagement in clinical practice guideline (CPG) development is recommended by multiple institutions and instruments measuring guideline quality. Approaches to engaging patients, however, vary between oversight organizations, quality tools and guideline developers. OBJECTIVE: We propose a ten-step framework outlining steps and options for patient engagement in guideline development with the goal of highlighting steps for patient engagement and methods by which this can be achieved. DISCUSSION: This framework provides a model for continuous patient engagement in CPGs by outlining ten steps of guideline development occurring at the levels of the developer/committee and the individual guideline project. At the developer level, patients can assist in topic nomination (step 1), topic prioritization (step 2) and guideline development group selection (step 3). Within specific guideline projects, patients' opinions may be incorporated when framing the question (step 4), creating an analytic framework and research plan (step 5), conducting the systematic review and conclusion formation (step 6), development of recommendations (step 7) and dissemination and implementation (step 8). At the end of process, patients can again be engaged at the developer level by helping determine when guidelines need updating (step 9) and evaluating the developer's approach to patient engagement (step 10). CONCLUSIONS: Patient engagement at each CPG development step has different purposes, mechanisms, advantages and disadvantages, and implications for resource utilization. This framework can serve as a resource for guideline developers desiring to increase patient engagement and reference for researchers investigating engagement methodology at different steps of the CPG lifecycle.

Naturalistic study of guideline implementation tool use via evaluation of website access and physician survey.

BACKGROUND: Clinical guidelines support decision-making at the point-of-care but the onus is often on individual users such as physicians to implement them. Research shows that the inclusion of implementation tools in or with guidelines (GItools) is associated with guideline use. However, there is little research on which GItools best support implementation by individual physicians. The purpose of this study was to investigate naturalistic access and use of GItools produced by the American Academy of Neurology (AAN) to inform future tool development. METHODS: Website accesses over six months were summarized for eight AAN guidelines and associated GItools published between July 2012 and August 2013. Academy members were surveyed about use of tools accompanying the sport concussion guideline. Data were analyzed using summary statistics and the Chi-square test. RESULTS: The clinician summary was accessed more frequently (29.0%, p < 0.001) compared with the slide presentation (26.8%), patient summary (23.2%) or case study (20.9%), although this varied by guideline topic. For the sport concussion guideline, which was accompanied by a greater variety of GItools, the mobile phone quick reference check application was most frequently accessed, followed by the clinician summary, patient summary, and slide presentation. For the sports concussion guideline survey, most respondents (response rate 21.8%, 168/797) were aware of the guideline (88.1%) and had read the guideline (78.6%). For GItool use, respondents indicated reading the reference card (51.2%), clinician summary (45.2%), patient summary (28.0%), mobile phone application (26.2%), and coach/athletic trainer summary (20.2%). Patterns of sports concussion GItool use were similar between respondents who said they had and had not yet implemented the guideline. CONCLUSIONS: Developers faced with resource limitations may wish to prioritize the development of printable or mobile application clinician summaries, which were accessed significantly more than other types of GItools. Further research is needed to understand how to optimize the design of such GItools.

Paraneoplastic autoantibody panels: sensitivity and specificity, a retrospective cohort.

BACKGROUND: Experts in the autoimmune paraneoplastic field recommend autoantibody testing as "panels" to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS. METHODS: A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes. RESULTS: Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17-53), specificity was 86% (95% CI: 81-90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection. CONCLUSION: This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing.

Postictal ammonia as a biomarker for electrographic convulsive seizures: A prospective study.

OBJECTIVE: Transient hyperammonemia (THA) was reported to follow generalized convulsions without sufficient evidence to confirm the epileptic nature of those events. We aimed to determine if postictal THA can differentiate between different types of events as confirmed electroencephalographically using video-electroencephalography (vEEG) monitoring. METHODS: In our prospective cohort, we screened all consented adults (>18 years) admitted to the epilepsy monitoring unit. Ammonia was checked at baseline, within 60 min of the event (for all patients) and 24 h after event (whenever possible). Patients were grouped into generalized convulsive seizures (GCS), psychogenic nonepileptic seizures with convulsions (PNES-C), or focal seizures (FS) based on vEEG. Data were analyzed using descriptive statistics and parametric/nonparametric methods. RESULTS: Of 78 patients enrolled, 13 had GCS, 8 had FS, and 9 had PNES-C. The groups were different with regard to gender (p = 0.04) and baseline ammonia (p = 0.02), but not age. The change in ammonia postictally from baseline was significantly different among the three groups (p = 0.004). The area under the receiver operator characteristic (ROC) curve for postictal ammonia to distinguish GCS from other groups was 0.88 (95% confidence interval [CI] 0.69-0.96) suggesting ammonia to be a good test differentiating epileptic GCS from other events. An ammonia level of ≥80 µmol/L correctly classified 80% of our patients (sensitivity 53.9%, specificity 100%). SIGNIFICANCE: Our results provide objective evidence for the association between THA and GCS seizures utilizing vEEG monitoring, and a basis for future studies to determine the role of postictal ammonia as an inexpensive diagnostic test to diagnose GCS.

Consensus statement: Using laryngeal electromyography for the diagnosis and treatment of vocal cord paralysis.

INTRODUCTION: The purpose of this study was to develop an evidence-based consensus statement regarding use of laryngeal electromyography (LEMG) for diagnosis and treatment of vocal fold paralysis after recurrent laryngeal neuropathy (RLN). METHODS: Two questions regarding LEMG were analyzed: (1) Does LEMG predict recovery in patients with acute unilateral or bilateral vocal fold paralysis? (2) Do LEMG findings change clinical management in these individuals? A systematic review was performed using American Academy of Neurology criteria for rating of diagnostic accuracy. RESULTS: Active voluntary motor unit potential recruitment and presence of polyphasic motor unit potentials within the first 6 months after lesion onset predicted recovery. Positive sharp waves and/or fibrillation potentials did not predict outcome. The presence of electrical synkinesis may decrease the likelihood of recovery, based on 1 published study. LEMG altered clinical management by changing the initial diagnosis from RLN in 48% of cases. Cricoarytenoid fixation and superior laryngeal neuropathy were the most common other diagnoses observed. CONCLUSIONS: If prognostic information is required in a patient with vocal fold paralysis that is more than 4 weeks and less than 6 months in duration, then LEMG should be performed. LEMG may be performed to clarify treatment decisions for vocal fold immobility that is presumed to be caused by RLN. Muscle Nerve 53: 850-855, 2016.

The Impact of Social Media on Dissemination and Implementation of Clinical Practice Guidelines: A Longitudinal Observational Study.

BACKGROUND: Evidence-based clinical practice guidelines (CPGs) are statements that provide recommendations to optimize patient care for a specific clinical problem or question. Merely reading a guideline rarely leads to implementation of recommendations. The American Academy of Neurology (AAN) has a formal process of guideline development and dissemination. The last few years have seen a burgeoning of social media such as Facebook, Twitter, and LinkedIn, and newer methods of dissemination such as podcasts and webinars. The role of these media in guideline dissemination has not been studied. Systematic evaluation of dissemination methods and comparison of the effectiveness of newer methods with traditional methods is not available. It is also not known whether specific dissemination methods may be more effectively targeted to specific audiences. OBJECTIVE: Our aim was to (1) develop an innovative dissemination strategy by adding social media-based dissemination methods to traditional methods for the AAN clinical practice guidelines "Complementary and alternative medicine in multiple sclerosis" ("CAM in MS") and (2) evaluate whether the addition of social media outreach improves awareness of the CPG and knowledge of CPG recommendations, and affects implementation of those recommendations. METHODS: Outcomes were measured by four surveys in each of the two target populations: patients and physicians/clinicians ("physicians"). The primary outcome was the difference in participants' intent to discuss use of complementary and alternative medicine (CAM) with their physicians or patients, respectively, after novel dissemination, as compared with that after traditional dissemination. Secondary outcomes were changes in awareness of the CPG, knowledge of CPG content, and behavior regarding CAM use in multiple sclerosis (MS). RESULTS: Response rates were 25.08% (622/2480) for physicians and 43.5% (348/800) for patients. Awareness of the CPG increased after traditional dissemination (absolute difference, 95% confidence interval: physicians 36%, 95% CI 25-46, and patients 10%, 95% CI 1-11) but did not increase further after novel dissemination (physicians 0%, 95% CI -11 to 11, and patients -4%, 95% CI -6 to 14). Intent to discuss CAM also increased after traditional dissemination but did not change after novel dissemination (traditional: physicians 12%, 95% CI 2-22, and patients 19%, 95% CI 3-33; novel: physicians 11%, 95% CI -1 to -21, and patients -8%, 95% CI -22 to 8). Knowledge of CPG recommendations and behavior regarding CAM use in MS did not change after either traditional dissemination or novel dissemination. CONCLUSIONS: Social media-based dissemination methods did not confer additional benefit over print-, email-, and Internet-based methods in increasing CPG awareness and changing intent in physicians or patients. Research on audience selection, message formatting, and message delivery is required to utilize Web 2.0 technologies optimally for dissemination.

New Onset Seizures in Hospitalized COVID-19 Patients; A Systematic Review and Meta-Analysis.

Objective: Seizures in COVID-19 patients continue to be a common reason for consulting the neurology service in the inpatient setting. This paper assesses the frequency of new onset seizures in adult hospitalized COVID-19 patients. Method: PubMed and EMBASE were searched, with fifteen cohort studies identified to calculate the primary outcome, which was the frequency of new onset seizures in hospitalized COVID-19 patients. An inverse variance meta-analysis of single proportions with a random effects model was applied to these cohort studies to calculate the primary outcome. Risk of bias in individual studies was assessed using the 10-item risk of bias tool for prevalence studies. Results: The meta-analysis revealed a frequency of .71% (95% confidential interval: .32-1.25, I2 = 89%, 147/28242 patients) for acute symptomatic seizures in patients with COVID-19. For secondary outcomes, the risk of seizures in patients who had EEG completed was 8.49% (95% confidential interval: .62-24.07, I2 = 14%, 44/535 patients). Slightly less than half of patients with COVID-19 and seizures were reported to have acute imaging abnormalities (45.7%) with acute vascular insults being commonly reported. Only a small percentage of COVID-19 patients with seizures (2.8%) met the criteria for COVID-19 encephalitis as determined by the international encephalitis consortium. Conclusion: The frequency of seizures in COVID-19 was .71% (95% confidential interval: .32-1.25). Slightly less than half of COVID-19 patients had head imaging abnormalities as a complication of COVID-19 infection. Only a small percentage of patients with seizures and COVID-19 met the criteria for COVID-19 encephalitis.

Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.

BACKGROUND: Lowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition. METHODS: This is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms. RESULTS: Mean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention. CONCLUSIONS: Intensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP.

Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline.

BACKGROUND AND OBJECTIVES: The purpose of this guideline is to update the 2010 American Academy of Neurology (AAN) brain death/death by neurologic criteria (BD/DNC) guideline for adults and the 2011 American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine guideline for infants and children and to clarify the BD/DNC determination process by integrating guidance for adults and children into a single guideline. Updates in this guideline include guidance related to conducting the BD/DNC evaluation in the context of extracorporeal membrane oxygenation, targeted temperature management, and primary infratentorial injury. METHODS: A panel of experts from multiple medical societies developed BD/DNC recommendations. Because of the lack of high-quality evidence on the subject, a novel, evidence-informed formal consensus process was used. This process relied on the panel experts' review and detailed knowledge of the literature surrounding BD/DNC to guide the development of preliminary recommendations. Recommendations were formulated and voted on, using a modified Delphi process, according to the 2017 AAN Clinical Practice Guideline Process Manual. MAJOR RECOMMENDATIONS: Eighty-five recommendations were developed on the following: (1) general principles for the BD/DNC evaluation, (2) qualifications to perform BD/DNC evaluations, (3) prerequisites for BD/DNC determination, (4) components of the BD/DNC neurologic examination, (5) apnea testing as part of the BD/DNC evaluation, (6) ancillary testing as part of the BD/DNC evaluation, and (7) special considerations for BD/DNC determination.

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.

Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary: Report of the AAN Guideline Subcommittee.

OBJECTIVE: To update the 2011 American Academy of Neurology (AAN) guideline on the treatment of painful diabetic neuropathy (PDN) with a focus on topical and oral medications and medical class effects. METHODS: The authors systematically searched the literature from January 2008 to April 2020 using a structured review process to classify the evidence and develop practice recommendations using the AAN 2017 Clinical Practice Guideline Process Manual. RESULTS: Gabapentinoids (standardized mean difference [SMD] 0.44; 95% confidence interval [CI], 0.21-0.67), serotonin-norepinephrine reuptake inhibitors (SNRIs) (SMD 0.47; 95% CI, 0.34-0.60), sodium channel blockers (SMD 0.56; 95% CI, 0.25-0.87), and SNRI/opioid dual mechanism agents (SMD 0.62; 95% CI, 0.38-0.86) all have comparable effect sizes just above or just below our cutoff for a medium effect size (SMD 0.5). Tricyclic antidepressants (TCAs) (SMD 0.95; 95% CI, 0.15-1.8) have a large effect size, but this result is tempered by a low confidence in the estimate. RECOMMENDATIONS SUMMARY: Clinicians should assess patients with diabetes for PDN (Level B) and those with PDN for concurrent mood and sleep disorders (Level B). In patients with PDN, clinicians should offer TCAs, SNRIs, gabapentinoids, and/or sodium channel blockers to reduce pain (Level B) and consider factors other than efficacy (Level B). Clinicians should offer patients a trial of medication from a different effective class when they do not achieve meaningful improvement or experience significant adverse effects with the initial therapeutic class (Level B) and not use opioids for the treatment of PDN (Level B).

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Diagnostic Yield of TEE in Patients with Cryptogenic Stroke and TIA with Normal TTE: A Systematic Review and Meta-Analysis.

INTRODUCTION: The role of transesophageal echocardiography (TEE) in cryptogenic stroke and transient ischemic attack (TIA) with normal transthoracic echocardiography (TTE) remains controversial in the absence of definite guidelines. We aimed to perform a systematic review and meta-analysis to estimate an additional diagnostic yield and clinical impact of TEE in patients with cryptogenic stroke and TIA with normal TTE. METHODS: We performed a systematic review of cohort studies on PubMed using the keywords 'cryptogenic stroke', cryptogenic TIA', 'TEE', and 'TTE' with matching MeSH terms. We included studies with patients who had cryptogenic stroke or TIA and had normal TTE findings, where the study intended to obtain TEE on all patients and reported all TEE abnormalities. The studies containing patients with atrial fibrillation were excluded. All studies were evaluated for internal and external validity. Inverse variance random effects models were used to calculate the effect size, the number needed to diagnose, and the 95% confidence interval. RESULTS: We included 15 studies with 2054 patients and found LA/LAA/aortic thrombus, valvular vegetation, PFO-ASA, valvular abnormalities, and complex aortic plaques on TEE. Of these, 37.5% (29.7%-45.1%) of patients had additional cardiac findings on TEE. Management of 13.6% (8.1%-19.1%) of patients had changed after TEE evaluation. Based on current guidelines, it should change management in 4.1% (2.1%-6.2%) of patients and could potentially change management in 30.4% (21.9%-38.9%) of patients. Sensitivity analysis was also performed with only class II studies to increase internal validity, which showed additional cardiac findings in 38.4% (28.5%-48.3%), changed management in 20.2% (8.7%-31.8%), should change management in 4.7% (1.5%-7.9%), and could potentially change management in 30.4% (17.8%-43.0%) of patients. CONCLUSIONS: The diagnostic yield of TEE to find any additional cardiac findings in patients with cryptogenic stroke or TIA is not only high, but it can also change management for certain cardiac abnormalities. TTE in cryptogenic stroke or TIA may mitigate future risks by tailoring the management of these patients.