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There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Some causes of spastic paraplegia are treatable and many are not. Diagnostic work-up to determine the etiology can be costly and invasive. Here we report the case of a man with slowly progressive spastic paraparesis. Using a multigene next-generation sequencing (NGS) panel, we identified a novel variant in the consensus splice site of the SPAST gene (exon 13, c.1536G>A, heterozygous), affecting codon 512 of the SPAST mRNA. The observed variant segregated with the disease in four tested family members. In this case, genetic confirmation obviated the need for additional testing such as MRI and lumbar puncture and helped the patient and his family understand his condition and prognosis. We conclude with a brief discussion of the SPG4/SPAST gene and the role of multigene panels in the diagnosis and management of hereditary spastic paraplegia.

Brain death has been accepted as a legal definition of death in most countries, but practices for determining brain death vary widely. One source of variation is in the use of ancillary tests to assist in the diagnosis of brain death. Through case-based discussions with 3 experts from 3 continents, this article discusses selected aspects of brain death, with a focus on the use of ancillary tests. In particular, we explore the following questions: Are ancillary tests necessary, or is the clinical examination sufficient? What ancillary tests are preferred, and under which circumstances? Are ancillary tests required when the primary mechanism of injury is brainstem injury? Should the family's wishes play a role in the need for ancillary tests? The same case-based questions were posed to the rest of our readership in an online survey, the preliminary results of which are also presented.

Background Minorities have historically been underrepresented in clinical research trials despite having comparatively poor health indicators. Recognizing the dual inequalities of increased disease burden and decreased research participation, the National Institute of Health (NIH) Revitalization Act of 1993 mandated the inclusion and reporting of women and minorities in NIH-funded research. While progress has been made in the subsequent decades, this underrepresentation of minorities in research trials persists and has been documented in multiple disciplines. However, the extent of adequate representation and reporting of minority inclusion in clinical trials for migraine remains unknown. Objectives In this systematic review and study, we review the literature examining the representation of women and minorities in migraine clinical research trials Methods First we searched PubMed for pertinent articles examining the inclusion of women and minorities in migraine clinical research trials. Second, we identified controlled-trials for migraine published since 2011 in major neurology, headache, and general medicine journals using the terms “migraine randomized controlled trial.” We then reviewed the results manually and excluded pilot studies and those with fewer than 50 participants. We next determined (a) how frequently representation of minorities and women were reported in these major trials; (b) what factors correlated with reporting; and (c) whether women and minority inclusion comprised their ratios in the general population. Results We identified 128 relevant clinical trials, of which 36 met our inclusion criteria. All 36 trials (100%) reported gender frequency, and 25 of 36 (69.4%) reported ethnicity or race. Among all studies, women and Whites represented 84.2 and 82.9% of participants (mean), respectively. Studies conducted in the United States and funded by a private company were more likely to report race than studies conducted exclusively outside of the U.S. or with a public sponsor. No studies stratified efficacy or safety by ethnicity or gender. Men and non-Whites in the U.S. were statistically underrepresented. Conclusions Most recent headache studies comply with the NIH mandate to include women and minorities in research trials, particularly U.S.-based and industry-funded studies. Whites are overrepresented compared to both the general population and the population of migraineurs. Future studies should strive to increase minority participation and investigate race-based differences in migraine expression, treatment response, and medication toxicity.

Drs. Ahlawat and Narayanaswami1 detailed the extent of industry-related financial interests among neurologists captured in the Open Payments (OP) database. Industry-related conflicts of interests (COIs) widely influence neurologic education, research, and clinical practice.2 Industry-funded trials often reach different conclusions than non-industry-funded trials,3 and even small gifts to physicians can influence their prescribing practices.4 Despite the OP database's shortcomings,5 it is an important step for 2 reasons. First, disclosure only mitigates COI if the disclosed information is widely and publicly available. Patients are generally not aware of their doctors' financial relationships.6 We hope OP will improve transparency. Second, the resulting social pressure from this transparency could lead to divestment from financial COI. Full disclosure is an important step towards mitigating COI, but does not redress subconscious biases that nearly invariably accompany financial relationships2; COI avoidance is often preferable. To investigate OP's effects on divestiture, we reviewed all neurologists in OP from 2013 to 2016. Of 9,505 neurologists in 2013 (OP's first year), 13 (0.07%) had ownership or investment interests totaling $26,610,645 (mean $2,800; median $65,975; maximum $24,949,811. In 2016, 16 of 11,105 neurologists had ownership and investment interest (0.09%) totaling $2,103,947 (mean $191; median $41,497; maximum $700,521). Perhaps OP is having an effect, but more research is required.

Objectives To compare outcomes between two models of acute ischemic stroke care. Namely 1) “drip-and-stay”, i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) “drip-and-ship”, i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) “hub”, i.e. tPA and subsequent treatment at a hub hospital. Materials and Methods We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method. Results Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98–1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64–1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73–1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0–1, sICH) were non-inferior when compared to the combined group. Conclusions Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.

Objective: To determine the safety of domperidone in the treatment of nausea associated with dihydroergotamine (DHE) infusion and headache. Methods: We audited our use of domperidone for the inpatient management of nausea, focusing on known safety concerns, particularly potential cardiac arrhythmias. Results: We reviewed 103 consecutive admissions of 90 patients admitted for IV DHE by infusion. Most admissions were to treat chronic migraine with (n = 53) or without (n = 46) aura. Domperidone was administered in 85 of 103 encounters and was well-tolerated at doses up to 80 mg/d. A significant side effect, akathisia, was observed in one patient. Baseline ECG with corrected QT interval (QTc) was obtained on all patients. Repeat ECG after domperidone was obtained in 21 patients, whose baseline characteristics did not differ from the group as a whole. ECG was interpreted blindly by a cardiac electrophysiologist. QTc did not differ before and after domperidone administration (Wilcoxon signed-rank test, median [interquartile range] 435.0 [410.5–453.0] at admission and 427.0 [399.0–452.5] after domperidone; p = 0.15). In combination with other antiemetics, domperidone was effective in treating nausea such that no patients had refractory nausea severe enough to limit DHE dose. Conclusions: This retrospective audit demonstrates that domperidone is safe in the treatment of nausea associated with inpatient DHE infusion and headache. While larger prospective trials are necessary to confirm these results and assess efficacy, current evidence and clinical experience suggests that domperidone is safe and useful for nausea and headache management. Classification of evidence: This study provides Class IV evidence that for patients with headache undergoing DHE infusion, domperidone is safe and effective in the treatment of nausea.

Magnetic resonance neurography (MRN) is an important tool to detect abnormalities of peripheral nerves. This pictorial review demonstrates the MRN features of a variety of neuropathies affecting the lumbosacral plexus (LSP) and lower extremity nerves, drawn from over 1200 MRNs from our institution and supplemented by the literature. Abnormalities can be due to spinal compression, extraspinal compression, malignancy, musculoskeletal disease, iatrogenesis, inflammation, infection, and idiopathic disorders. We discuss indications and limitations of MRN in diagnosing LSP neuropathies. As MRN becomes more widely used, physicians must become familiar with the differential diagnosis of abnormalities detectable with MRN of the LSP.

Psychogenic nonepileptic seizures (PNES) are relatively common, accounting for 5-40% of visits to tertiary epilepsy centers. Inpatient video-electroencephalogram (vEEG) monitoring is the gold standard for diagnosis, but additional positive predictive tools are necessary given vEEG's relatively scarce availability. In this study, we investigated if the number of patient-reported allergies distinguishes between PNES and epilepsy. Excessive allergy-reporting, like PNES, may reflect somatization. Using electronic medical records, ICD-9 codes, and text-identification algorithms to search EEG reports, we identified 905 cases of confirmed PNES and 5187 controls with epilepsy but no PNES. Patients with PNES averaged more self-reported allergies than patients with epilepsy alone (1.93 vs. 1.00, p

A conflict of interest (COI) exists when a physician's professional responsibilities are compromised by personal or financial relationships. COIs between physicians and the pharmaceutical or medical device industry (Industry) are common. Collaborations with Industry have many potential benefits, but also raise potential ethical pitfalls. Industry-related COIs have widespread influence on medical education, research, and clinical practice, and therefore have profound implications for the integrity of the field of medicine. Full disclosure is an important step toward mitigating COI but does not redress subconscious accompanying biases. I review the spectrum of potential COI faced by physicians, with a focus on the ethics surrounding the relationship between neurologists and Industry. Other financial and nonfinancial COIs that influence neurologists and nonindividual entities, such as academic institutions, medical journals, and professional societies, are also discussed. Solutions ranging from disclosure to avoidance and recusal are briefly considered.

Background HIV-associated neurocognitive disorders (HAND) remain problematic even in the antiretroviral therapy (ART) era. Efavirenz (EFV) is well known for neuropsychiatric side effects and has been associated with worsening neurocognitive performance (NC). We hypothesized that switching from an ART regimen with EFV to one with rilpivirine (RPV) would improve NC. Methods This single-center, open-label, superiority, randomized controlled trial was conducted at Maharaj Nakorn Chiang Mai Hospital June 2018 to March 2019. HIV- infected adults (≥18 years), virologically suppressed on an EFV-containing regimen for at least 12 months, who met Frascati’s criteria of asymptomatic neurocognitive impairment (ANI), were randomized to a switching arm (RPV-containing regimen) vs. a control arm (EFV-containing regimen). The primary objective was to compare the improvement of NC at month 6 (M6) after switching. Secondary outcomes were individual NC domains, tolerability, and safety after switching regimens. Results 20 ANI participants (10 per group) completed the study. 11 participants showed NC improvement at M6: 6 in the switching arm and 5 in the control arm. Global neuro deficit scores (GDS), figure learning, and figure memory at M6 significantly improved in both arms (P < 0.05). Verbal memory and speed of information processing improved over time in the switching arm only (0.6 (0.1–1.0); P = 0.02, and 0.7 (0.1–1.2); P = 0.03, respectively). However, no significant differences between the two groups were observed. Male gender, age < 50 and initiation of ART within 5 years after diagnosis all trended toward an association with improved NC. No tolerability issues or clinical significant adverse events were reported. Conclusion Despite some positive trends, switching from an EFV-containing regimen did not significantly improve NC. This finding was consistent with previous reports. A larger study with longer follow-up may be warranted. Disclosures All authors: No reported disclosures.

I read with interest Llinas et al.1's article that discussed burnout and resiliency. I appreciate the authors' emphasis on the primacy of systemic changes to address the problem, such as increasing opportunities for recognition and rewarding activities.

In the article “BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis,” Sebok et al. reported similar sensitivity of blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) in detecting crossed cerebellar diaschisis (CCD) as compared to (15O)-H2O-PET in 25 participants with symptomatic unilateral cerebrovascular steno-occlusive disease and reported that those with CCD had poorer baseline neurologic performance and 3-month neurologic outcome. In response, Reidler et al. question whether CCD was the cause of consequence of poor outcomes, noting that it may be an epiphenomenon of large-volume supratentorial strokes and citing conflicting evidence in the literature about independent association of CCD with post-stroke outcomes. They suggest accounting for lesion volume and distribution in the analyses. In their reply, Niftrik et al. agree that their finding of worse outcome in those with CCD should be cautiously interpreted and investigated in follow-up studies, but argue that supratentorial stroke volume is an inexact measurement, although stroke location would be helpful to examine. They clarify their finding of impaired supratentorial BOLD-CVR in the group with CCD and opine that hemodynamic changes may cause CCD rather than just functional disruption.

I applaud the Brain Death Working Group for working toward uniform standards for determination of brain death.1

Multifocal motor neuropathy (MMN) is a rare neuropathy that is often treatable with immunomodulatory therapy if diagnosed early. However, accurate diagnosis is difficult due to a significant overlap of symptoms with other neurological conditions, such as amyotrophic lateral sclerosis (ALS). Evidence of immunoglobulin M (IgM) anti-ganglioside GM1 antibodies and electrodiagnostic findings of conduction block are useful diagnostic criteria for MMN but are not universal findings. This review explores the differential diagnosis of MMN and ALS and discusses three cases of MMN initially diagnosed as ALS, in which the correct diagnosis allowed effective treatment. These cases highlight the need for greater awareness of MMN among physicians.

Objective:The mechanism of hypoglycorrhachia—low CSF glucose—in meningitis remains unknown. We sought to evaluate the relative contribution of CSF inflammation vs microorganisms (bacteria and fungi) in lowering CSF glucose levels.Methods:We retrospectively categorized CSF profiles into microbial and aseptic meningitis and analyzed CSF leukocyte count, glucose, and protein concentrations. We assessed the relationship between these markers using multivariate and stratified linear regression analysis for initial and repeated CSF sampling. We also calculated the receiver operating characteristics of CSF glucose and CSF-to-serum glucose ratios to presumptively diagnose microbial meningitis.Results:We found that increasing levels of CSF inflammation were associated with decreased CSF glucose levels in the microbial but not aseptic category. Moreover, elevated CSF protein levels correlated more strongly than the leukocyte count with low CSF glucose levels on initial (R2= 36%,p< 0.001) and repeated CSF sampling (R2= 46%,p< 0.001). Hypoglycorrhachia (Conclusions:The main driver of hypoglycorrhachia appears to be a combination of microbial meningitis with moderate to high degrees of CSF inflammation and proteins, suggesting that the presence of microorganisms capable of catabolizing glucose is a determinant of hypoglycorrhachia in meningitis. A major notable exception is neurosarcoidosis. Low CSF glucose and CSF-to-serum glucose ratios are useful markers for the diagnosis of microbial meningitis.