Faculty Bibliography

Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.

INTRODUCTION:Optical coherence tomography (OCT)-derived peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell+inner plexiform layer (GCIPL) thickness inter-eye differences (IEDs) are robust measurements for identifying clinical history acute ON in people with MS (PwMS). This study investigated the utility and durability of these measures as longitudinal markers to identify optic nerve lesions. METHODS:Prospective, multi-center international study of PwMS (with/without clinical history of ON) and healthy controls. Data from two sites in the International MS Visual System Consortium (IMSVISUAL) were analyzed. Mixed-effects models were used to compare inter-eye differences based on MS and acute ON history. RESULTS:Average age of those with MS (n = 210) was 39.1 ± 10.8 and 190 (91%) were relapsing-remitting. Fifty-nine (28.1%) had a history of acute unilateral ON, while 9/210 (4.3%) had >1 IB episode. Median follow-up between OCT scans was 9 months. By mixed-effects modeling, IEDs were stable between first and last visits within groups for GCIPL for controls (p = 0.18), all PwMS (p = 0.74), PwMs without ON (p = 0.22), and PwMS with ON (p = 0.48). For pRNFL, IEDs were within controls (p = 0.10), all PwMS (p = 0.53), PwMS without ON history (p = 0.98), and PwMS with history of ON (p = 0.81). CONCLUSION:We demonstrated longitudinal stability of pRNFL and GCIPL IEDs as markers for optic nerve lesions in PwMS, thus reinforcing the role for OCT in demonstrating optic nerve lesions.

Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) expressed at birth with profound sensory loss and early death. The FD founder mutation in the ELP1 gene arose within the Ashkenazi Jews in the sixteenth century and is present in 1:30 Jews of European ancestry. The mutation yield a tissue-specific skipping of exon 20 and a loss of function of the elongator-1 protein (ELP1), which is essential for the development and survival of neurons. Patients with FD produce variable amounts of ELP1 in different tissues, with the brain producing mostly mutant transcripts. Patients have excessive blood pressure variability due to the failure of the IXth and Xth cranial nerves to carry baroreceptor signals. Neurogenic dysphagia causes frequent aspiration leading to chronic pulmonary disease. Characteristic hyperadrenergic "autonomic crises" consisting of brisk episodes of severe hypertension, tachycardia, skin blotching, retching, and vomiting occur in all patients. Progressive features of the disease include retinal nerve fiber loss and blindness, and proprioceptive ataxia with severe gait impairment. Chemoreflex failure may explain the high frequency of sudden death in sleep. Although 99.5% of patients are homozygous for the founder mutation, phenotypic severity varies, suggesting that modifier genes impact expression. Medical management is currently symptomatic and preventive. Disease-modifying therapies are close to clinical testing. Endpoints to measure efficacy have been developed, and the ELP1 levels are a good surrogate endpoint for target engagement. Early intervention may be critical for treatment to be successful.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.

OBJECTIVE:To determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. METHODS:We examined thirteen healthy controls and sixteen mildly to moderately impaired chronic stroke patients. We used transcranial magnetic stimulation (TMS) to probe TI from the contralesional onto ipsilesional hemisphere (assigned in controls). We recorded the ipsilateral silent period in the paretic biceps (BIC) and first dorsal interosseous (FDI). We measured TI strength, distribution gradient (TI difference between muscles), and motor impairment (Fugl-Meyer Assessment). RESULTS:Both groups had stronger TI acting on their FDIs than BICs (p < 0.001). However, stroke patients also had stronger TI acting on their BICs than controls (p = 0.034), resulting in a flatter distribution of inhibition (p = 0.028). In patients, stronger FDI inhibition correlated with less hand impairment (p = 0.031); BIC inhibition was not correlated to impairment. CONCLUSION/CONCLUSIONS:TI is more evenly distributed to the paretic FDI and BIC in chronic stroke. The relative increase in proximal inhibition does not relate to better function, as it does distally. SIGNIFICANCE/CONCLUSIONS:The results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.

PURPOSE:The term "brainstem death" is ambiguous; it can be used to refer either exclusively to loss of function of the brainstem or loss of function of the whole brain. We aimed to establish the term's intended meaning in national protocols for the determination of brain death/death by neurologic criteria (BD/DNC) from around the world. METHODS:Of 78 unique international protocols on determination of BD/DNC, we identified eight that referred exclusively to loss of function of the brainstem in the definition of death. Each protocol was reviewed to ascertain whether it 1) required assessment for loss of function of the whole brain, 2) required assessment only for loss of function of the brainstem, or 3) was ambiguous about whether loss of function of the higher brain was required to declare DNC. RESULTS:Of the eight protocols, two (25%) required assessment for loss of function of the whole brain, three (37.5%) only required assessment for loss of function of the brainstem, and three (37.5%) were ambiguous about whether loss of function of the higher brain was required to declare death. The overall agreement between raters was 94% (κ = 0.91). CONCLUSIONS:There is international variability in the intended meaning of the terms "brainstem death" and "whole brain death" resulting in ambiguity and potentially inaccurate or inconsistent diagnosis. Regardless of the nomenclature, we advocate for national protocols to be clear regarding any requirement for ancillary testing in cases of primary infratentorial brain injury who may fulfill clinical criteria for BD/DNC.

BACKGROUND:Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS:This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS:A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS:Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

PURPOSE/UNASSIGNED:Visual impairment-related disabilities have become increasingly pervasive. Current reports estimate a total of 36 million persons with blindness and 217 million persons with moderate to severe visual impairment worldwide. Assistive technologies (AT), including text-to-speech software, navigational/spatial guides, and object recognition tools have the capacity to improve the lives of people with blindness and low vision. However, access to such AT is constrained by high costs and implementation barriers. More recently, expansive growth in mobile computing has enabled many technologies to be translated into mobile applications. As a result, a marketplace of accessibility apps has become available, yet no framework exists to facilitate navigation of this voluminous space. MATERIALS AND METHODS/UNASSIGNED:We developed the BLV (Blind and Low Vision) App Arcade: a fun, engaging, and searchable curated repository of app AT broken down into 11 categories spanning a wide variety of themes from entertainment to navigation. Additionally, a standardized evaluation metric was formalized to assess each app in five key dimensions: reputability, privacy, data sharing, effectiveness, and ease of use/accessibility. In this paper, we describe the methodological approaches, considerations, and metrics used to find, store and score mobile applications. CONCLUSION/UNASSIGNED:The development of a comprehensive and standardized database of apps with a scoring rubric has the potential to increase access to reputable tools for the visually impaired community, especially for those in low- and middle-income demographics, who may have access to mobile devices but otherwise have limited access to more expensive technologies or services.

BACKGROUND:Analyses of factors that determine quality of perinatal care consistently rely on clinical markers, while failing to assess experiential outcomes. Understanding how model of care and birth setting influence experiences of respect, autonomy, and decision making, is essential for comprehensive assessment of quality. METHODS:We examined responses (n = 1771) to an online cross-sectional national survey capturing experiences of perinatal care in the United States. We used validated patient-oriented measures and scales to assess four domains of experience: (1) decision-making, (2) respect, (3) mistreatment, and (4) time spent during visits. We categorized the provider type and birth setting into three groups: midwife at community birth, midwife at hospital-birth, and physician at hospital-birth. For each group, we used multivariate logistic regression, adjusted for demographic and clinical characteristics, to estimate the odds of experiential outcomes in all the four domains. RESULTS:Compared to those cared for by physicians in hospitals, individuals cared for by midwives in community settings had more than five times the odds of experiencing higher autonomy (aOR: 5.22, 95% CI: 3.65-7.45), higher respect (aOR: 5.39, 95% CI: 3.72-7.82) and lower odds of mistreatment (aOR: 0.16, 95% CI: 0.10-0.26). We found significant differences across birth settings: participants cared for by midwives in the community settings had significantly better experiential outcomes than those in the hospital settings: high- autonomy (aOR: 2.97, 95% CI: 2.66-4.27), respect (aOR: 4.15, 95% CI: 2.81-6.14), mistreatment (aOR: 0.20, 95% CI: 0.11-0.34), time spent (aOR: 8.06, 95% CI: 4.26-15.28). CONCLUSION/CONCLUSIONS:Participants reported better experiential outcomes when cared for by midwives than by physicians. And for those receiving midwifery care, the quality of experiential outcomes was significantly higher in community settings than in hospital settings. Care settings matter and structures of hospital-based care may impair implementation of the person-centered midwifery care model.

Neurologists in both the inpatient and outpatient settings are increasingly using ultrasound to diagnose and manage common neurological diseases. Advantages include cost-effectiveness, the lack of exposure to ionizing radiation, and the ability to perform at the bedside to provide real-time data. There is a growing body of literature that supports using ultrasonography to improve diagnostic accuracy and aid in performing procedures. Despite the increasing utilization of this imaging modality in medicine, there has been no comprehensive review of the clinical applications of ultrasound in the field of neurology. We discuss the current uses and limitations of ultrasound for various neurological conditions. We review the role for ultrasound in commonly performed neurologic procedures including lumbar puncture, botulinum toxin injections, nerve blocks, and trigger point injections. We specifically discuss the technique for ultrasound-assisted lumbar puncture and occipital nerve block as these are commonly performed. We then focus on the utility of ultrasound in the diagnosis of neurologic conditions. This includes neuromuscular diseases such as motor neuron disorders, focal neuropathies, and muscular dystrophy as well as vascular conditions such as stroke and vasospasm in subarachnoid hemorrhage. We also address ultrasound's use in critically ill patients to aid in identifying increased intracranial pressure, hemodynamics, and arterial and/or venous catheterization. Finally, we address the importance of standardized ultrasound curricula in trainee education and make recommendations for the future directions of research and competency guidelines within our specialty.