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.

Improving pharmacy performance through market orientation and the implementation of expanded pharmacy services.

This study seeks to extend the limited knowledge of market orientation's effects in retail pharmacy. Specifically, this study explores market orientation's role in the implementation of expanded pharmacy services and resulting performance implications among Canadian retail pharmacies. The results of the structural equation model showed that market orientation directly influenced the implementation of expanded pharmacy services and professional performance. The implementation of expanded pharmacy services was linked to professional performance and ultimately furthered financial performance. This study highlights the importance of how a market-oriented strategy and a pharmacy's decision to implement expanded pharmacy services can increase the dual objectives of the retail pharmacy.

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.

Arterial anatomy of the anterior abdominal wall: Ultrasound evaluation as a real-time guide to percutaneous instrumentation.

INTRODUCTION: Instrumenting the anterior abdominal wall carries a potential for vascular trauma. We previously assessed the presence, position, and size of the anterior abdominal wall superior and inferior (deep) epigastric arteries with computed tomography (CT). We now present a study using ultrasound (US) assessment of these arteries, to evaluate its use for real time guidance of percutaneous procedures involving the rectus sheath. MATERIALS AND METHODS: Twenty-four participants (mean age 67.9 ± 9 years, 15 M:9 F [62:38%]) were assessed with US at three axial planes on the anterior abdominal wall: transpyloric plane (TPP), umbilicus, and anterior superior iliac spine (ASIS). RESULTS: An artery was visible least frequently at the TPP (62.5 - 45.8%), compared with the umbilicus (95.8-100%) and ASIS (100%), on the left, χ2 (2) = 20.571; p < .001, and right, χ2 (2) = 27.842; p < .001, with a moderate strength association (Cramer's V = 0.535 [left] and 0.622 [right]). Arteries were most commonly observed within the rectus abdominis muscle at the level of the TPP and umbilicus, but posterior to the muscle at the level of the ASIS (95.8-100%). As with the CT study, the inferior epigastric artery was observed to be larger in diameter, start more laterally, and move medially as it coursed superiorly. CONCLUSIONS: These data corroborate our previous results and suggest that the safest level to instrument the rectus sheath (with respect to vascular anatomy) is at the TPP. Such information may be particularly relevant to anesthetists performing rectus sheath block and surgeons during laparoscopic port insertion.

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.

A marking of the cricothyroid membrane with extended neck returns to correct position after neck manipulation and repositioning.

BACKGROUND: Emergency front of neck airway access by anaesthetists carries a high failure rate and it is recommended to identify the cricothyroid membrane before induction of anaesthesia in patients with a predicted difficult airway. We have investigated whether a marking of the cricothyroid membrane done in the extended neck position remains correct after the patient's neck has been manipulated and subsequently repositioned. METHODS: The subject was first placed in the extended head and neck position and had the cricothyroid membrane identified and marked with 3 methods, palpation, 'laryngeal handshake' and ultrasonography and the distance from the suprasternal notch to the cricothyroid membrane was measured. The subject then moved off the table and sat on a chair and subsequently returned to the extended neck position and examinations were repeated. RESULTS: Skin markings of all 11 subjects lay within the boundaries of the cricothyroid membrane when the subject was repositioned back to the extended neck position and the median difference between the two measurements of the distance from the suprasternal notch was 0 mm (range 0-2 mm). CONCLUSION: The cricothyroid membrane can be identified and marked with the subject in the extended neck position. Then the patient's position can be changed as needed, for example to the 'sniffing' neck position for conventional intubation. If a front of neck airway access is required during subsequent airway management, the patient can be returned expediently to the extended-neck position, and the marking of the centre of the membrane will still be in the correct place.

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.

Stakeholders' Perspectives on Preclinical Testing for Alzheimer's Disease.

BACKGROUND AND AIMS: Progress towards validating amyloid beta as an early indicator of Alzheimer's disease (AD) heightens the need for evaluation of stakeholders' perspectives of the benefits and harms of preclinical testing in asymptomatic individuals. METHODS: Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD. RESULTS: Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, and psychological harms. Nine participants reported either a "positive global perspective" or a "positive global perspective (qualified)." CONCLUSION: Results from this study characterized stakeholders' perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research.

A perspective on the evidence for glymphatic obstruction in spaceflight associated neuro-ocular syndrome and fatigue.

Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. Previously, the current authors have discussed the similarities and differences between SANS and idiopathic intracranial hypertension to try to elucidate a possible pathophysiology. Recently, a theory has been advanced that SANS may occur secondary to failure of the glymphatic system caused by venous dilatation within the brain and optic nerves. There is recent evidence to suggest glymphatic obstruction occurs in childhood hydrocephalus, multiple sclerosis and syringomyelia due to venous outflow dilatation similar to that proposed in SANS. The purpose of the current paper is to discuss the similarities and differences between the known CSF and venous pathophysiology in SANS with these other terrestrial diseases, to see if they can shed any further light on the underlying cause of this microgravity-induced disease.

A lumped parameter modelling study of cerebral autoregulation in normal pressure hydrocephalus suggests the brain chooses to be ischemic.

Normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and an ischemic metabolic state. Ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. There is evidence of some retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox. A lumped parameter model was developed utilizing the known limits of autoregulation in man. The model was tested by predicting the cerebral blood volume changes which would be brought about by changes in resistance. NPH and the post shunt state were then modeled using the known constraints provided from the literature. The model successfully predicted the cerebral blood volume changes brought about by altering the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial resistance decreased after modelling shunt insertion. The model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate.

Computational Fluid Dynamic Simulation of the Cerebral Venous System in Multiple Sclerosis and Control Patients: Are Hemodynamic Variances Evident in Multiple Sclerosis?

OBJECTIVE: An investigation was performed to determine the relevant hemodynamic parameters which could help assess vascular pathology in human diseases. Using these parameters, this study aims to assess if there are any hemodynamic differences in the cerebral veins of multiple sclerosis (MS) patients and controls which could impact the etiology of MS. METHODS: 40 MS participants and 20 controls were recruited for this study. Magnetic resonance imaging (MRI) was performed to enable 3D geometries of the anatomy and the blood flow rates at the boundaries to be computed. Computational fluid dynamics (CFD) models were created for each participant and simulated using patient-specific boundary conditions. RESULTS: The pressure drop and vascular resistance did not significantly differ between the groups. The internal jugular vein (IJV) cross-sectional area was larger in the MS group (Right IJV: p = 0.04, Left IJV: p = 0.02) and the straight sinus (ST) flow rate was higher in MS across all ages (p = 0.005) compared to controls. Vascular resistance was shown to indicate regions in the cerebral veins which could correspond to increased venous pressure. Conclusion & Significance: This study shows that the pressure and vascular resistance of the cerebral veins are unlikely to be directly related to the etiology of MS. The finding of higher ST flow could correspond to increased inflammation in the deep venous system. Resistance as a measure of vascular pathology shows promise and could be useful to holistically investigate blood flow hemodynamics in a variety of other diseases of the circulatory system.

Syringomyelia Is Associated with a Reduction in Spinal Canal Compliance, Venous Outflow Dilatation and Glymphatic Fluid Obstruction.

The cause of the cystic dilatation of the cord found in syringomyelia has been a source of conjecture for a considerable time. Recent studies have shown that there is a reduction in craniospinal compliance in both childhood hydrocephalus and multiple sclerosis which leads to venous outflow dilatation. Both diseases are associated with glymphatic outflow obstruction. Venous dilatation will narrow the perivenous glymphatic outflow pathway and lead to an increase in glymphatic outflow resistance. Syringomyelia has been shown to be associated with reduced spinal canal compliance. This paper discusses the possibility that venous dilatation and obstructed glymphatic outflow within the cord may be behind the cystic dilatation found within syringomyelia.

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.