Determination of Brain Death in Patients Undergoing Short-Term Mechanical Circulatory Support Devices.

OBJECTIVE: To describe apnoea test (AT) and ancillary study performance for brain death (BD) determination among patients undergoing short-term mechanical circulatory support (MCS) devices, including extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP). METHODS: We retrospectively analysed data regarding use of AT and ancillary study in consecutive adult patients who were diagnosed with BD while on MCS devices (including ECMO and IABP) over a 10-year period. RESULTS: Out of 140 patients, eight were on MCS devices at the time of BD (four ECMO, two ECMO and IABP, two IABP). The most common aetiology of BD was hypoxic ischaemic brain injury (6/8, 75%). In four patients (50%), the AT was not attempted because of haemodynamic instability and ECMO; in the remaining four (50%), both AT and ancillary studies were used. In three patients on ECMO, AT was performed by reducing the ECMO sweep flow rate to a range 0.5-2.7 L/min in order to achieve hypercarbia. One patient underwent AT while on IABP which was complicated by hypotension. All patients underwent ancillary tests, most commonly transcranial Doppler ultrasonography (TCD) (7/8, 88%); among those, cerebral circulatory arrest was confirmed in six of seven patients (86%), all of whom had left ventricular ejection fracture (LVEF) ≥20% and/or were supported with IABP. CONCLUSIONS: There are multiple uncertainties regarding BD diagnosis while on MCS, prompting the need for ancillary studies in most patients. Our study shows that TCD can be used to support BD diagnosis in patients on ECMO who have sufficient cardiac contractility and/or IABP to produce pulsatile flow. TCD use in ECMO patients low LVEF needs further study.

Outcomes, Time-Trends, and Factors Associated With Ancillary Study Use for the Determination of Brain Death.

OBJECTIVES: Brain death determination often requires ancillary studies when clinical determination cannot be fully or safely completed. We aimed to analyze the results of ancillary studies, the factors associated with ancillary study performance, and the changes over time in number of studies performed at an academic health system. DESIGN: Retrospective cohort. SETTING: Multihospital academic health system. PATIENTS: Consecutive adult patients declared brain dead between 2010 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 140 brain death patients, ancillary studies were performed in 84 (60%). The false negative rate of all ancillary studies was 4% (5% of transcranial Doppler ultrasounds, 4% of nuclear studies, 0% of electroencephalograms, and 17% of CT angiography). In univariate analysis, ancillary study use was associated with female sex (odds ratio, 2.4; 95% CI, 1.21-5.01; p = 0.013) and the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 2.9; 95% CI, 1.43-5.88; p = 0.003), nontraumatic intracranial hemorrhage (odds ratio, 0.45; 95% CI, 0.21-0.96; p = 0.039), or traumatic brain injury (odds ratio, 0.22; 95% CI, 0.04-0.8; p = 0.031). In multivariable analysis, female sex (odds ratio, 5.7; 95% CI, 2.56-15.86; p = 0.004), the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 3.2; 95% CI, 1.3-8.8; p = 0.015), and the neurologists performing brain death declaration (odds ratio, 0.08; 95% CI, 0.004-0.64; p = 0.034) were factors independently associated with use of ancillary studies. Over the study period, the total number of ancillary studies performed each year did not significantly change; however, the number of electroencephalograms significantly decreased with time (odds ratio per 1-yr increase, 0.67; 95% CI, 0.49-0.90; p = 0.014). CONCLUSIONS: A large number of ancillary studies were performed despite a clinical determination of brain death; patients with hypoxic-ischemic brain injury are more likely to undergo ancillary studies for brain death determination, and neurologists were less likely to use ancillary studies for brain death. Recently, the use of electroencephalograms for brain death determination has decreased, likely reflecting significant concerns regarding its validity and reliability.

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

Diagnosis and Treatment of Multiple Sclerosis: A Review.

Importance: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. Observations: MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid-specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. Conclusions and Relevance: MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.

Asymmetric cerebral edema presenting with severe neurologic impairment and seizures after cardiac and thoracic interventions.

INTRODUCTION: A syndrome of focal neurologic deficits with characteristic imaging features, acute encephalopathy, and seizures after cardiac and thoracic interventions has been previously briefly reported in the literature. In a retrospective observational study, we aim to identify the prevalence and characteristics of this syndrome, in addition to discussing the possible underlying pathophysiology. METHODS: In a retrospective study, we reviewed records of consecutive adult patients (≥18 years old) who underwent cardiac and thoracic procedures at a single institution between September 2014 to September 2019 and found to have evidence of focal cerebral edema following their procedure. We included and reported clinical course of patients who developed post-operative neurologic dysfunction and underwent magnetic resonance imaging (MRI) showing (1) asymmetric cerebral edema with (2) cortical diffusion restriction and (3) T2 cortical or subcortical hyperintensity and (4) no proximal vascular occlusion. RESULTS: Three out of 107 patients (2.8%) met our inclusion criteria. These represented one male and two females with age at presentation of 63, 81 and 69, respectively. All patients developed severe neurologic impairment on the same day following their procedure (sternotomy with valve or bypass surgery in 2 patients; esophageal dilatation procedure in 1 patient). All patients underwent MRI of the brain and vessel imaging qualifying our inclusion criteria. Two patients improved neurologically prior to discharge, and one patient expired after family elected to withdraw care. CONCLUSION: We present a series of cases with a rare syndrome after cardiac and thoracic interventions. Although the exact mechanism of this syndrome remains unclear, we believe it to be related to relative cerebral hyperperfusion and cerebral dysautoregulation following anesthesia and thoracic manipulation. Future studies should focus on understanding the true prevalence and pathophysiology of this syndrome.

Cerebral Microhemorrhage and Purpuric Rash in COVID-19: The Case for a Secondary Microangiopathy.

INTRODUCTION: Since the emergence of Coronavirus Disease 19 (COVID-19) pandemic, multiple neurologic complications in infected patients have been reported. Despite these reports, the mechanism of COVID-19 nervous system injury is not well understood. We report the case of a COVID-19 patient with diffuse microhemorrhages on brain MRI, positive anticardiolipin antibodies, and purpuric rash with biopsy showing a thrombotic vasculopathy, all features suggestive of secondary microangiopathy. CASE REPORT: A 69-year-old male with history of hypertension, chronic kidney disease, and hypothyroidism presented with one week of dyspnea, cough, diarrhea, and fevers. Chest x-ray demonstrated bibasilar consolidations and nasopharyngeal reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. He had subsequent respiratory decline requiring intubation the day after admission. He developed a truncal morbilliform rash and diffuse purpura, a biopsy of which showed small dermal blood vessels with intraluminal microthrombi consistent with thrombotic vasculopathy. He was found to have elevated aCL IgM and IgG and equivocal lupus anticoagulant study. Brain MRI obtained for persistent encephalopathy showed innumerable areas of susceptibility weighted imaging changes throughout the bilateral juxtacortical white matter, corpus callosum, basal ganglia, and brainstem, as well as multiple small areas of FLAIR hyperintensities, consistent with microhemorrhage DISCUSSION: While there have been several reported cases of neurologic manifestations of COVID-19, the pathophysiology may not be related to neurotropism of the virus itself. The new development of antiphospholipid antibodies and thrombotic vasculopathy in dermal blood vessels in this patient suggest a secondary microangiopathy potentially related to a virally-induced inflammatory state.

Clinical experience of seropositive ganglionic acetylcholine receptor antibody in a tertiary neurology referral center.

INTRODUCTION: Antibody against the acetylcholine receptor of autonomic ganglia (gAChR-Ab) is implicated in the pathogenesis of autoimmune autonomic ganglionopathy (AAG) and several other disorders. METHODS: This study was a retrospective evaluation of 95 patients positive for gAChR-Ab. RESULTS: Twenty-one (22%) patients had AAG, with a greater median gAChR-Ab level (0.21 nmol/L) and higher percentage (57%) of antibody levels >0.20 nmol/L when compared with the remaining 74 patients without autonomic manifestations (non-AAG group, 0.10 nmol/L and 15%, respectively). Only 2 new cases of malignancy were diagnosed after gAChR-Ab detection. The non-AAG group was associated with high frequencies of neurological and non-neurological autoimmunity, but also included 23 (31%) patients with mostly degenerative disorders. CONCLUSION: Detection of gAChR-Ab, especially at a higher level, is helpful for the diagnosis of AAG in patients with corresponding autonomic symptoms. However, its value is limited for predicting cancer risk and for diagnosis and management of patients without autonomic symptoms.

Chronic cerebrospinal venous insufficiency: pitfalls and perils of sonographic assessment.

OBJECTIVES: Duplex sonography has been proposed as a diagnostic modality for detection of chronic cerebrovascular venous insufficiency, a recently proposed hypothesis of multiple sclerosis (MS) pathogenesis. We reviewed potential challenges of duplex sonography for diagnosis of chronic cerebrovascular venous insufficiency and used interim pooled data from a study aimed to apply cerebrovascular venous insufficiency criteria to a group of patients with MS and control patients without MS. METHODS: Duplex sonography for chronic cerebrovascular venous insufficiency was performed in patients with MS and controls. Extracranial and deep cerebral veins were studied by using a published chronic cerebrovascular venous insufficiency protocol and criteria. Comparative imaging was performed to explore how physiologic factors and imaging techniques could affect key parameters. The effects of varying definitions on fulfilling chronic cerebrovascular venous insufficiency diagnostic criteria were also explored. RESULTS: Forty-two patients were enrolled. Twenty-five (60%) had a reduction in internal jugular vein cross-sectional area by 50% or more, cross-sectional area of 0.3 cm(2) or less, and/or a B-mode abnormality. No patients had reflux longer than 0.88 seconds in both sitting and supine positions, the presence of duplex sonographic reflux on transcranial Doppler imaging, or a larger internal jugular vein cross-sectional area in the sitting versus supine position. Fourteen patients (33.3%) had either a flap or septum, and 1 had a web. Collateral veins to the vertebral veins were identified in 14 of 42 patients (33.3%). The use of transcranial Doppler imaging versus quality Doppler profiles resulted in fewer patients meeting criteria for chronic cerebrovascular venous insufficiency. CONCLUSIONS: There are several important variables, including physiologic, technical, and criterion definitions, in the application of sonographic assessment of chronic cerebrovascular venous insufficiency that may affect diagnostic accuracy.

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.

Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality.

OPINION STATEMENT: Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord. Traditionally, MS has been considered an autoimmune disorder, with the primary pathophysiology arising from an errant immune system. Recent work has raised the possibility that MS is not caused primarily by an immune abnormality but may instead arise from venous anomalies affecting the jugular and/or azygos venous systems. This condition has been called chronic cerebrospinal venous insufficiency (CCSVI). It has been proposed that CCSVI may be pathogenic in MS, causing venous back pressure and iron deposition, with a secondary immune response. Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies. There is intense interest and ongoing work to evaluate the presence of venous anomalies in MS patients as well as in normal controls and patients with other neurologic conditions; to characterize such anomalies, if present; and to further understand whether the concept of a "backpressure" pathology is borne out by the evidence. If CCSVI is indeed a pathogenic mechanism for some subset of the MS population, this would dramatically change the focus of attention for therapeutic endeavors and monitoring for this population and would bring MS therapeutics firmly into the area of vascular intervention. On the other hand, the history of MS research contains many novel and potentially paradigm-shifting ideas that were later disproved by other investigators.

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).

Antibody-mediated autoimmune encephalitis: A practical approach.

Antibody-mediated autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders. Symptoms typically include subacute, progressive neuropsychiatric symptoms with associated cognitive dysfunction, movement disorders, and autoimmune seizures. The diagnosis should be based on objective neurologic dysfunction in combination with auto antibody testing. Treatment with immunotherapies requires both short-term and long-term strategies depending on the specific syndrome and potential for relapse. In this paper, we review key features of AE, focusing on syndromes involving cell surface and synaptic proteins, and share a practical approach to the diagnosis and management, including common pitfalls associated with nonspecific antibody findings.

The effect of incorporating an arterial pH target during apnea test for brain death determination.

BACKGROUND: Persistent apnea despite an adequate rise in arterial pressure of CO2 is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO2 threshold) on brain death declarations. METHODS: We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed. RESULTS: Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation [SD] 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO2 (47 vs 145, p < 0.01), and a lower PaCO2 (55 vs 73, p = 0.01). Among patients with a positive AT using PaCO2 threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87). CONCLUSION: Implementing a BD criteria requiring both arterial pH and PaCO2 thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.

Timing of Acute Stroke in COVID-19-A Health System Registry Study.

BACKGROUND AND PURPOSE: The association between SARS-CoV-2 infection and stroke remains unknown. We aimed to compare the characteristics of stroke patients who were hospitalized with Coronavirus Disease 2019 (COVID-19) based on the timing of stroke diagnosis. METHODS: We performed a retrospective analysis of adult patients in a health system registry of COVID-19 who were hospitalized and had imaging-confirmed acute stroke during hospitalization. Baseline characteristics and hospital outcomes were collected and analyzed. RESULTS: Out of 882 COVID-19 patients who were hospitalized between March 9 to May 17, 2020, 14 patients (2% of all COVID-19 patients and 21% of those who underwent imaging) presented with stroke or developed stroke during hospitalization. Eleven had acute ischemic stroke (AIS) and 3 had acute hemorrhagic stroke. Six patients (43%) presented to the hospital with acute stroke symptoms and were found to have SARS-CoV-2. Compared to patients who presented with AIS, more patients with AIS during hospitalization were male, of older age, had pneumonia and acute respiratory distress syndrome, were severely ill, and had high inflammatory and thrombotic markers (including C reactive protein, D dimer, ferritin, and fibrinogen). Among all patients, hospital mortality was high (50%) and the majority of patients who were discharged had poor neurological outcome. CONCLUSIONS: A distinction should be made between patients who present with acute stroke with concurrent SARS-CoV-2 infection and those who develop stroke as a complication of severe COVID-19. It is likely that a subset of stroke patients will incidentally test positive for the virus given the widespread pandemic.

Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy.

BACKGROUND: Multiple sclerosis (MS) is usually considered a 'young persons' disease', typically presenting between the ages of 20 and 40. In this study we review our experience with patients diagnosed at age 60 or over, with particular emphasis on patients who continue to have evidence of active inflammation despite a later onset. METHODS: We reviewed all cases of MS diagnosed at or over age 60 in our center over a 5-year period. We identified 111 patients and recorded their clinical and imaging characteristics using prespecified variables. Analyses were performed to describe their interval to diagnosis, clinical syndromes, imaging and laboratory characteristics. RESULTS: At the time of diagnosis, 8% of patients had a clinically isolated syndrome, 33% were in the relapsing-remitting stage, while 23% had a secondary progressive course, and 32% were primary progressive. Eighty-eight percent of patients had a brain MRI judged 'typical for MS', and 32% of all patients receiving gadolinium had enhanced lesions. Forty-six percent of patients with relapsing-remitting MS or clinically isolated syndrome exhibited gadolinium enhancement. Myelitis was the most common initial clinical syndrome, and progressive myelopathy was a common but not exclusive clinical syndrome at the time of diagnosis. CONCLUSIONS: A relapsing pattern of MS is not uncommon, even in patients diagnosed over the age of 60. Active inflammation (clinical relapses and gadolinium enhancement) occurs in a significant number of patients with MS with later diagnosis. These observations have implications for evaluation and treatment of patients with MS presenting at an older age.

Brain death evaluation during the pandemic.

Coronavirus disease 2019 (COVID-19) may pose unique challenges to clinicians attempting to diagnose brain death in patients infected with the SARS-CoV-2. Among these challenges is the risk of aerosol generation during the traditional apnea testing using the insufflation technique in addition to the risk of complications due to SARS-CoV-2-related lung disease. In this article, we discuss these challenges and provide further guidance to minimize such risks to ensure safety of healthcare professionals and other patients. We also emphasize the importance of maintaining the standards of brain death determination in this critical time.

Technology-enabled assessments to enhance multiple sclerosis clinical care and research.

BACKGROUND: Comprehensive and efficient assessments are necessary for clinical care and research in chronic diseases. Our objective was to assess the implementation of a technology-enabled tool in MS practice. METHOD: We analyzed prospectively collected longitudinal data from routine multiple sclerosis (MS) visits between September 2015 and May 2018. The MS Performance Test, comprising patient-reported outcome measures (PROMs) and neuroperformance tests (NPTs) self-administered using a tablet, was integrated into routine care. Descriptive statistics, Spearman correlations, and linear mixed-effect models were used to examine the implementation process and relationship between patient characteristics and completion of assessments. RESULTS: A total of 8022 follow-up visits from 4199 patients (median age 49.9 [40.2-58.8] years, 32.1% progressive course, and median disease duration 13.6 [5.9-22.3] years) were analyzed. By the end of integration, the tablet version of the Timed 25-Foot Walk was obtained in 89.0% of patients and the 9-Hole Peg Test in 94.8% compared with 74.2% and 64.3%, respectively before implementation. The greatest increase in data capture occurred in processing speed and low-contrast acuity assessments (0% prior vs 78.4% and 36.7%, respectively, following implementation). Four PROMs were administered in 41%-98% of patients compared with a single depression questionnaire with a previous capture rate of 70.6%. Completion rates and time required to complete each NPT improved with subsequent visits. Younger age and lower disability scores were associated with shorter completion time and higher completion rates. CONCLUSIONS: Integration of technology-enabled data capture in routine clinical practice allows acquisition of comprehensive standardized data for use in patient care and clinical research.

Incorporating Clinical Practice Guidelines and Quality Measures Into High-Quality Cost-Effective Care for Patients With Multiple Sclerosis.

This article presents a hypothetical case of a patient with multiple sclerosis (MS), reviewing the use of clinical practice guidelines and incorporation of quality measures into practice. Appropriate diagnosis of MS is important to avoid the cost and consequences of a misdiagnosis. Ensuring that treatment discussion occurs when a patient with MS is receptive is good clinical practice and a guideline recommendation from the American Academy of Neurology. Continuing dialogue about disease-modifying therapy and ongoing monitoring are important for patient care and improved outcomes. Ultimately, cost-effective care in MS relates to using appropriate medicines in patients with active MS, ensuring adherence, and careful monitoring.