Faculty Bibliography

Effective diagnosis, prognostication, and management of CNS malignancies traditionally involves invasive brain biopsies that pose significant risk to the patient. Sampling and molecular profiling of cerebrospinal fluid (CSF) is a safer, rapid, and noninvasive alternative that offers a snapshot of the intracranial milieu while overcoming the challenge of sampling error that plagues conventional brain biopsy. Although numerous biomarkers have been identified, translational challenges remain, and standardization of protocols is necessary. Here, we systematically reviewed 141 studies (Medline, SCOPUS, and Biosis databases; between January 2000 and September 29, 2022) that molecularly profiled CSF from adults with brain malignancies including glioma, brain metastasis, and primary and secondary CNS lymphomas. We provide an overview of promising CSF biomarkers, propose CSF reporting guidelines, and discuss the various considerations that go into biomarker discovery, including the influence of blood-brain barrier disruption, cell of origin, and site of CSF acquisition (eg, lumbar and ventricular). We also performed a meta-analysis of proteomic data sets, identifying biomarkers in CNS malignancies and establishing a resource for the research community.

OBJECTIVES/OBJECTIVE:When administered in repeated daily doses, transcranial direct current stimulation (tDCS) directed to the prefrontal cortex has cumulative efficacy for the treatment of depression. Depression can be marked by altered processing of emotionally salient information. An acute marker of response to tDCS may be measured as an immediate change in emotional information processing. Using an easily administered web-based task, we tested immediate changes in emotional information processing in acute response to tDCS in participants with and without depression. MATERIALS AND METHODS/METHODS:We enrolled n = 21 women with mild-to-moderate depression and n = 20 controls without depression to complete a web-based visual search task before and after 30 minutes of tDCS directed to the prefrontal cortex. The timed task required participants to identify a target face among arrays showing sad, neutral, or mixed (distractor) expressions. RESULTS:At baseline, as predicted, the participants with depression differed from those without in emotional processing speed (mean z score difference -0.66 ± 0.27, p = 0.022) and accuracy in identifying sad stimuli (error rate: 4.4% vs 1.8%, p = 0.039). In response to tDCS, the participants with depression became significantly faster on the distractor condition (pre- vs post-tDCS z scores: -0.45 ± 0.65 vs -0.85 ± 0.65, p = 0.009), suggesting a specific reduction in bias toward negative emotional information. In response to tDCS, the depressed group also had significant improvements in self-reported mood (increased happy, decreased sad and anxious mood). CONCLUSIONS:Participants with depression vs those without were differentiated by their performance of the visual search task at baseline and in response to tDCS. Given that measurable effects on depression scales may require weeks of tDCS treatments, acute change in emotional information processing can serve as an easily obtainable marker of depression and its response to tDCS. CLINICAL TRIAL REGISTRATION/BACKGROUND:The Clinicaltrials.gov registration number for the study is NCT05188248.

Biofeedback has Grade A evidence for the treatment of migraine, yet few studies have examined the factors associated with patients' decisions to pursue biofeedback treatment recommendations. We sought to examine reasons for adherence or non-adherence to referral to biofeedback therapy as treatment for migraine. Patients with migraine who had been referred for biofeedback by a headache specialist/behavioral neurologist were interviewed in person or via Webex. Patients completed an enrollment questionnaire addressing demographics and questions related to their headache histories. At one month, patients were sent a follow-up questionnaire via REDCap and asked if they had pursued the recommendation for biofeedback therapy, their reasons for their decision, and their impressions about biofeedback for those who pursued it. Nearly two-thirds (65%; 33/51) of patients responded at one month. Of these, fewer than half (45%, 15/33) had contacted biofeedback providers, and only 18% (6/33) completed a biofeedback session. Common themes emerged for patients who did not pursue biofeedback, including feeling that they did not have time, concern for financial obstacles (e.g., treatment cost and/or insurance coverage), and having difficulty scheduling an appointment due to limited provider availability. When asked about their preference between type of biofeedback provider (e.g., a physical therapist or psychologist), qualitative responses were mixed; many patients indicated no preference as long as they took insurance and/or were experienced, while others indicated a specific preference for a physical therapist or psychologist due to familiarity, or prior experiences with that kind of provider. Patients with migraine referred for biofeedback therapy face numerous obstacles to pursuing treatment.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required. ANN NEUROL 2024.

The World Brain Death Project (WBDP) is a 2020 international consensus statement that provides historical background and recommendations on brain death/death by neurologic criteria (BD/DNC) determination. It addresses 13 topics including: (1) worldwide variance in BD/DNC, (2) the science of BD/DNC, (3) the concept of BD/DNC, (4) minimum clinical criteria for BD/DNC determination, (5) beyond minimum clinical BD/DNC determination, (6) pediatric and neonatal BD/DNC determination, (7) BD/DNC determination in patients on ECMO, (8) BD/DNC determination after treatment with targeted temperature management, (9) BD/DNC documentation, (10) qualification for and education on BD/DNC determination, (11) somatic support after BD/DNC for organ donation and other special circumstances, (12) religion and BD/DNC: managing requests to forego a BD/DNC evaluation or continue somatic support after BD/DNC, and (13) BD/DNC and the law. This review summarizes the WBDP content on each of these topics and highlights relevant work published from 2020 to 2023, including both the 192 citing publications and other publications on BD/DNC. Finally, it reviews questions for future research related to BD/DNC and emphasizes the need for national efforts to ensure the minimum standards for BD/DNC determination described in the WBDP are included in national BD/DNC guidelines and due consideration is given to the recommendations about social and legal aspects of BD/DNC determination.

BACKGROUND:The Uniform Law Commission paused work of the Drafting Committee to Revise the Uniform Determination of Death Act (UDDA) in September 2023. METHODS:Thematic review was performed of comments submitted to the Uniform Law Commission by medical organizations (MO), organ procurement organizations (OPO), and advocacy organizations (AO) from 1/1/2023 to 7/31/2023. RESULTS:Of comments from 41 organizations (22 AO, 15 MO, 4 OPO), 34 (83%) supported UDDA revision (50% OPO, 33% MO recommended against revision). The most comments addressed modifications to "all functions of the entire brain, including the brainstem" (31; 95% AO, 75% OPO, 47% MO), followed by irreversible versus permanent (25; 77% AO, 50% OPO, 40% MO), accommodation of brain death/death by neurologic criteria (BD/DNC) objections (23; 100% OPO, 80% MO, 32% AO), consent for BD/DNC evaluation (18; 75% OPO, 47% MO, 36% AO), "accepted medical standards" (13; 36% AO, 33% MO, 0% OPO), notification before BD/DNC evaluation (14; 100% OPO, 53% MO, 9% AO), time to gather before discontinuation of organ support after BD/DNC determination (12; 60% MO, 25% OPO, 9% AO), and BD/DNC examiner credential requirements (2; 13% MO, 0% AO, 0% OPO). The predominant themes were that the revised UDDA should include the term "irreversible" and shouldn't (1) stipulate specific medical guidelines, (2) require notification before BD/DNC evaluation, or (3) require time to gather before discontinuation of organ support after BD/DNC determination. Views on other topics were mixed, but MO and OPO generally advocated for the revised UDDA to take a functional approach to BD/DNC, not require consent for BD/DNC evaluation, and not require opt-out accommodation of BD/DNC objections. Contrastingly, many AO and some MO with religious affiliations or a focus on advocacy favored the revised UDDA take an anatomic approach to BD/DNC or eliminate BD/DNC altogether, require consent for BD/DNC evaluation, and require opt-out accommodation of BD/DNC objections. CONCLUSIONS:Most commenting organizations support UDDA revision, but perspectives on the approach vary, so the Drafting Committee could not formulate revisions that would be agreeable to all stakeholders.