Faculty Bibliography

ABSTRACT:A 62-year-old man presented with headache, fever, and malaise. He was diagnosed with Anaplasma phagocytophilum, confirmed by serum polymerase chain reaction, and started on oral doxycycline. After 5 days of treatment, the patient began to experience gait imbalance with frequent falls, as well as myoclonus, and confusion. Examination was notable for opsoclonus-myoclonus-ataxia (OMA) and hypometric saccades. Cerebrospinal fluid (CSF) autoimmune encephalitis panel demonstrated a markedly elevated neuronal intermediate filament (NIF) immunoglobulin G antibody titer of 1:16, with positive neurofilament light- and heavy-chain antibodies. These antibodies were suspected to have been triggered by the Anaplasma infection. Repeat CSF examination 8 days later still showed a positive immunofluorescence assay for NIF antibodies, but the CSF titer was now less than 1:2. Body computed tomography imaging was unrevealing for an underlying cancer. Our patient illustrates a postinfectious mechanism for OMA and saccadic hypometria after Anaplasma infection.

BACKGROUND:The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke. OBJECTIVE:To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort. METHODS:We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020. RESULTS:The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002). CONCLUSION/CONCLUSIONS:COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates.

BACKGROUND:The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS:We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS:We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS:The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

In 2017, the International League Against Epilepsy (ILAE) Classification of Epilepsies described the "genetic generalized epilepsies" (GGEs), which contained the "idiopathic generalized epilepsies" (IGEs). The goal of this paper is to delineate the four syndromes comprising the IGEs, namely childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We provide updated diagnostic criteria for these IGE syndromes determined by the expert consensus opinion of the ILAE's Task Force on Nosology and Definitions (2017-2021) and international external experts outside our Task Force. We incorporate current knowledge from recent advances in genetic, imaging, and electroencephalographic studies, together with current terminology and classification of seizures and epilepsies. Patients that do not fulfill criteria for one of these syndromes, but that have one, or a combination, of the following generalized seizure types: absence, myoclonic, tonic-clonic and myoclonic-tonic-clonic seizures, with 2.5-5.5 Hz generalized spike-wave should be classified as having GGE. Recognizing these four IGE syndromes as a special grouping among the GGEs is helpful, as they carry prognostic and therapeutic implications.

BACKGROUND:Brazil has been disproportionately affected by COVID-19, placing a high burden on ICUs. RESEARCH QUESTION/OBJECTIVE:Are perceptions of ICU resource availability associated with end-of-life decisions and burnout among health-care providers (HCPs) during COVID-19 surges in Brazil? METHODS:We electronically administered a survey to multidisciplinary ICU HCPs during two 2-week periods (in June 2020 and March 2021) coinciding with COVID-19 surges. We examined responses across geographical regions and performed multivariate regressions to explore factors associated with reports of: (1) families being allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19 and (2) emotional distress and burnout. RESULTS:We included 1,985 respondents (57% physicians, 14% nurses, 12% respiratory therapists, 16% other HCPs). More respondents reported shortages during the second surge compared with the first (P < .05 for all comparisons), including lower availability of intensivists (66% vs 42%), ICU nurses (53% vs 36%), ICU beds (68% vs 22%), and ventilators for patients with COVID-19 (80% vs 70%); shortages were highest in the North. One-quarter of HCPs reported that families were allowed less input in decisions about maintaining life-sustaining treatments for patients with COVID-19, which was associated with lack of intensivists (adjusted relative risk [aRR], 1.37; 95% CI, 1.05-1.80) and ICU beds (aRR, 1.71; 95% CI, 1.16-2.62) during the first surge and lack of N95 masks (aRR, 1.43; 95% CI, 1.10-1.85), noninvasive positive pressure ventilation (aRR, 1.56; 95% CI, 1.18-2.07), and oxygen concentrators (aRR, 1.50; 95% CI, 1.13-2.00) during the second surge. Burnout was higher during the second surge (60% vs 71%; P < .001), associated with witnessing colleagues at one's hospital contract COVID-19 during both surges (aRR, 1.55 [95% CI, 1.25-1.93] and 1.31 [95% CI, 1.11-1.55], respectively), as well as worries about finances (aRR, 1.28; 95% CI, 1.02-1.61) and lack of ICU nurses (aRR, 1.25; 95% CI, 1.02-1.53) during the first surge. CONCLUSIONS:During the COVID-19 pandemic, ICU HCPs in Brazil experienced substantial resource shortages, health-care disparities between regions, changes in end-of-life care associated with resource shortages, and high proportions of burnout.

OBJECTIVE:One of the clinical hallmarks of tuberous sclerosis complex (TSC) is radiologically identified cortical tubers, which are present in most patients. Intractable epilepsy may require surgery, often involving invasive diagnostic procedures such as intracranial electroencephalography (EEG). Identifying the location of the dominant tuber responsible for generating epileptic activities is a critical issue. However, the link between cortical tubers and epileptogenesis is poorly understood. Given this, we hypothesized that tuber voxel intensity may be an indicator of the dominant epileptogenic tuber. Also, via tuber segmentation based on deep learning, we explored whether an automatic quantification of the tuber burden is feasible. METHODS:We annotated tubers from structural magnetic resonance images across 29 TSC subjects, summarized tuber statistics in eight brain lobes, and determined suspected epileptogenic lobes from the same group using EEG monitoring data. Then, logistic regression analyses were performed to demonstrate the linkage between the statistics of cortical tuber and the epileptogenic zones. Furthermore, we tested the ability of a neural network to identify and quantify tuber burden. RESULTS:Logistic regression analyses showed that the volume and count of tubers per lobe, not the mean or variance of tuber voxel intensity, were positively correlated with electrophysiological data. In 47.6% of subjects, the lobe with the largest tuber volume concurred with the epileptic brain activity. A neural network model on the test dataset showed a sensitivity of .83 for localizing individual tubers. The predicted masks from the model correlated highly with the neurologist labels, and thus may be a useful tool for determining tuber burden and searching for the epileptogenic zone. SIGNIFICANCE:We have proven the feasibility of an automatic segmentation of tubers and a derivation of tuber burden across brain lobes. Our method may provide crucial insights regarding the treatment and outcome of TSC patients.

The Functional Activities Questionnaire (FAQ) is a collateral-report measure of difficulties in activities of daily living. Despite its widespread use, psychometric analyses have been limited in scope, piecemeal across samples, and limited primarily to classical test theory. This article consolidated and expanded psychometric analyses using tools from generalizability and item response theories among 27,916 individuals from the National Alzheimer's Coordinating Center database who completed the FAQ. Reliability was evaluated with internal consistency, test-retest, and generalizability analyses. Validity was assessed via convergence with neurocognitive measures, classification accuracy with impairment stage, and confirmatory factor and item response theory analyses. Demographics did not impact scores and there was strong evidence for reliability (0.52-0.95), though coefficients were attenuated when restricted in range to diagnostic groups (e.g., normal cognition). There were strong correlations with neurocognitive measures (rs: -.30 to -.59), strong classification accuracy (areas under the curve: .81-.99), and a single-factor model had excellent fit. All items evidenced strong item response theory discrimination and provided significant information regarding functional disability, albeit within a relatively restricted range. The FAQ is a reliable and valid measure of activities of daily living concerns for use in clinical/research settings. It best assesses mild levels of functional difficulty, which is helpful in distinguishing normal cognition from mild cognitive impairment and dementia.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.