Neurological applications of belzutifan in von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is a tumor predisposition syndrome caused by mutations in the VHL gene that presents with visceral neoplasms and growths, including clear cell renal cell carcinoma, and central nervous system manifestations, such as hemangioblastomas of the brain and spine. The pathophysiology involves dysregulation of oxygen sensing caused by the inability to degrade HIFα, leading to the overactivation of hypoxic pathways. Hemangioblastomas are the most common tumors in patients with VHL and cause significant morbidity. Until recently, there were no systemic therapies available for patients that could effectively reduce the size of these lesions. Belzutifan, the first approved HIF-2α inhibitor, has demonstrated benefit in VHL-associated tumors, with a 30% response rate in hemangioblastomas and ~30%-50% reduction in their sizes over the course of treatment. Anemia is the most prominent adverse effect, affecting 76%-90% of participants and sometimes requiring dose reduction or transfusion. Other significant adverse events include hypoxia and fatigue. Overall, belzutifan is well tolerated; however, long-term data on dosing regimens, safety, and fertility are not yet available. Belzutifan holds promise for the treatment of neurological manifestations of VHL and its utility may influence the clinical management paradigms for this patient population.

Patient Income Does Not Predict Disability or Mortality in Hospitalized COVID-19 Patients in a Large Health Care System in the Chicago Metropolitan Area.

Race, income, and their role in COVID-19 infection in the community have been extensively reported, but their impact on outcomes in hospitalized patients is less well defined. We retrospectively analyzed the first 509 COVID-19 patients in our hospital network, examining associations between median household income, 30-day mortality, and ambulatory state at discharge (using the modified Rankin scale (mRS)), adjusting for hospitalization at the academic medical center (AMC) and other variables. Income did not predict mortality. Higher income was associated with slightly increased odds of ability to ambulate at discharge only when accounting for hospital type. At the AMC, income and mortality were lower and functional outcomes more favorable. Patients with lower incomes had greater comorbidity burden. That income was not associated with measures of morbidity and mortality from COVID-19 is a remarkable and encouraging finding. Academic medical centers may mitigate detrimental effects of socioeconomic disparities on COVID-19 seen at the community level.

Persistent viral RNA shedding of SARS-CoV-2 is associated with delirium incidence and six-month mortality in hospitalized COVID-19 patients.

BACKGROUND: Persistent viral RNA shedding of SARS-CoV-2 following COVID-19 has increasingly been recognized, with limited understanding of its implications on outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively assessed for persistent viral shedding across Northwestern Medicine Healthcare (NMHC) patients between March and August 2020. We assessed for predictors of persistent viral shedding, in-hospital delirium, and six-month mortality using binary logistic regression. RESULTS: Of the 2,518 hospitalized patients with an RT-PCR-confirmed diagnosis of COVID-19, 959 underwent repeat SARS-CoV-2 RT-PCR at least fourteen days from initial positive testing. Of those, 405 (42.2%) patients were found to have persistent viral shedding. Persistent viral shedding was associated with male sex, increased BMI, diabetes mellitus, chronic kidney disease, and exposure to corticosteroids during initial COVID-19 hospitalization. Persistent viral shedding was independently associated with incidence of in-hospital delirium after adjusting for factors including severity of respiratory dysfunction (OR 2.45; 95% CI 1.75, 3.45). Even after adjusting for age, severity of respiratory dysfunction, and occurrence of in-hospital delirium, persistent viral shedding remained significantly associated with increased six-month mortality (OR 2.43; 95% CI 1.42, 4.29). CONCLUSIONS: Persistent viral shedding occurs frequently in hospitalized COVID-19 patients and is associated with in-hospital delirium and increased six-month mortality.

Clinical Usefulness of Genetic Testing For Patients with Moyamoya Disease: A Systematic Review.

BACKGROUND: The effect of genetic factors on presentation and outcomes of moyamoya disease (MMD) is unclear. We aimed to examine differences in presentation of MMD by genetic variant, delineate the influence of genetic factors on outcomes, and characterize the applicability of genetic testing to management. METHODS: A systematic review was conducted using the PubMed, Embase, and Scopus databases. Title/abstract screening, full-text screening, and data extraction were conducted. RESULTS: Of 1329 articles, 12 were included. Genes included RNF213 (ring finger protein 213), VEGF (vascular endothelial growth factor), and soluble VEGR receptor (sVEGFR) 1 and 2. Patients heterozygous and homozygous for the p.R1480K variant of RNF213 had younger age of onset; were more frequently familial, had posterior cerebral artery involvement, had bilateral lesions; and were more likely to present with cerebral infarction or transient ischemic attack. The heterozygous p.4810K variant is associated with improved postoperative collateral formation. Stroke recurrence, stroke-free survival, neurologic status, and functional condition after surgery are not associated with the p.4180K genotype. Patients homozygous for p.4180K more frequently experience long-term cognitive impairment. Patients with the C/C genotype of VEGF 2634 or decreased sVEGFR-1 and sVEGFR levels postoperatively had greater postoperative collateral formation. CONCLUSIONS: Genetic factors correlate with MMD presentation including age of onset, severity, and symptoms, and angiographic and clinical outcomes after surgery. Incorporation of genetic testing panels into practice may allow for risk stratification, management, and follow-up of children and adults with MMD. However, future studies are necessary to validate the usefulness of genetic testing for MMD before this situation occurs.

Acute-care hospital reencounters in COVID-19 patients.

Acute-care hospital reencounters (ACHEs)-encompassing emergency department visits, observation stays, and hospital readmissions-following COVID-19 hospitalization may exacerbate health care system strain and impair recovery from illness. We sought to characterize these reencounters and factors associated with reencounters. We identified the first consecutive 509 patients hospitalized for COVID-19 within an IL hospital network, and examined ACHEs, experienced within 30 days and 4 months of index hospitalization. We identified independent predictors of reencounter using binary logistic regression. Of 509 patients, 466 (91.6%) were discharged alive from index COVID-19 hospitalization. Within 30 days and 4 months, 12.4% and 21.5% of patients, respectively, experienced ACHEs. The median time to first ACHE was 24.2 (IQR 6.5, 55) days. COVID-19 symptom exacerbation was the leading reason for early ACHE (44.8%). Reencounters, both within 30 days and 4 months, were associated with a history of a neurological disorder before COVID-19 (OR 2.78 [95% CI 1.53, 5.03] and OR 2.75 [95% CI 1.67, 4.53], respectively). Older patients and those with diabetes mellitus, chronic obstructive pulmonary disease, or organ transplantation tended towards more frequent ACHEs. Steroid treatment during COVID-19 hospitalization demonstrated reduced odds of 30-day reencounter (OR 0.31 [95% CI 0.091, 0.79]). Forty-nine patients had repeat SARS-CoV-2 nasopharyngeal testing during a reencounter; twelve (24.5%) patients had positive reencounter tests and experienced more frequent reencounters than those testing negative. COVID-19 symptom exacerbation is a leading cause of early ACHE after COVID-19 hospitalization, and steroid use during index hospitalization may reduce early reencounters. Neurologic illness before COVID-19 predicts ACHEs.

Abnormal movements in hospitalized COVID-19 patients: A case series.

BACKGROUND: Abnormal movements in Covid-19 patients have been reported with varying degree of frequency, prompting neurologic consultation and additional diagnostic evaluation. We sought to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation. METHODS: We retrospectively analyzed the first 50 consecutive patients with confirmed Covid-19 hospitalized at our tertiary medical care center who underwent acute inpatient neurology consultation from March 2020 through May 2020. Indication for neurologic consultation and diagnostic studies performed were identified by electronic medical record review. RESULTS: Of the 50 initial consultation requests, 11 (22.0%) patients were evaluated for abnormal movements (nine male and two female). Myoclonus was diagnosed in 6/11 (54.5%) patients. Additionally, two patients were diagnosed with seizures (confirmed on EEG in one), while two additional patients were diagnosed with tremor (physiologic and probable functional). A single case of serotonin syndrome was also identified. CONCLUSION: Abnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent type of abnormal movement observed. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.

Incidence of catheter-associated right atrial thrombus detected by transthoracic echocardiogram.

INTRODUCTION: The development of right atrial (RA) thrombus (RAT) is a known complication of central venous catheter insertion (CVC). Deeper insertion of CVC within the RA may increase the risk for RAT development versus those placed at the superior vena cava (SVC)-RA junction. We sought to evaluate the incidence of catheter-associated RAT as detected by transthoracic echocardiograms (TTEs), characterize thrombi though multimodal imaging, and evaluate thrombi management with follow-up imaging. METHODS: A retrospective analysis was conducted of consecutive TTEs from our institution between October 1, 2018, and January 1, 2020, in which a venous catheter was visualized in the RA. Studies were reviewed in detail to determine the presence of suspected RAT. Demographic data, comorbidities, laboratory values, characteristics of the catheter and the thrombus, subsequent imaging and management, and outcomes were collected. RESULTS: A total of 364 TTEs were performed in 290 patients with a venous catheter visualized in the RA. Of these 290 patients, 15 had an imaging suspicion for RAT yielding an incidence of 5.2%. Management strategies included anticoagulation in 13 (86.7%) patients and catheter removal in 11 (73.3%) patients. At eight months of follow-up, 11 (73.3%) patients had resolution of RAT based on subsequent imaging. CONCLUSION: In patients with deeply placed CVC catheters, the incidental detection of RAT by TTE was not trivial. Anticoagulation and catheter removal and replacement, if deemed safe, were effective methods of thrombus management. RAT as a complication of CVCs must be accounted for when addressing factors that influence depth of CVC insertion.

Social Media in Neurosurgery: A Systematic Review.

OBJECTIVE: Social media has been used increasingly in neurosurgery by individuals. We aimed to identify demographics and preferences of social media use, describe the scope of social media use, and characterize its utility. METHODS: A systematic review was conducted using PubMed, Embase, and Scopus databases. Titles and abstracts from articles identified in the search were read and selected for full-text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for relevant data. RESULTS: Of 431 resultant articles, 29 were included. Patients and caregivers most commonly used Facebook and Twitter, whereas nearly 50% of neurosurgeons used LinkedIn and Doximity. Patient and caregiver users of social media tended to be <35 years old. Content of posts varied from requesting/providing information (∼40%) to seeking emotional support/forming connections (∼30%). A total of 20.6% of videos were irrelevant to clinical neurosurgery. Factual accuracy of most videos was poor to inadequate. Social media use was associated with greater academic impact for neurosurgical departments and journals. Posts with photos and videos and weekend posts generated 1.2-2 times greater engagement. CONCLUSIONS: Patients and caregivers who use social media are typically younger than 35 years old and commonly use Facebook or Twitter. Neurosurgeons prefer Doximity and LinkedIn. Social media yields information regarding common symptoms and uncovers novel symptoms. Videos are poor-to-inadequate quality and often irrelevant to clinical neurosurgery. Optimizing social media use will augment the exchange of ideas regarding clinical practice and research and empower patients and caregivers.

Transcranial Doppler Ultrasound Evidence of Active Cerebral Embolization in COVID-19.

OBJECTIVE: To report six consecutive patients with confirmed coronavirus disease-2019 (COVID-19) who underwent Transcranial Doppler (TCD) ultrasonography evaluation for cerebral microemboli in the setting of suspected or confirmed acute ischemic stroke. METHODS: Patient data were obtained from medical records from Northwestern Memorial Hospital, Chicago, IL between May and June 2020. All patients with confirmed COVID-19 who underwent clinical TCD ultrasonography for microemboli detection were included. RESULTS: A total of eight TCD studies were performed in six patients with COVID-19 (4 men and 2 women, median age 65±5), four with confirmed ischemic stroke and two with refractory encephalopathy. Microemboli were detected in three male patients, two patients had suffered a confirmed ischemic stroke and one who developed prolonged encephalopathy. Microemboli of varying intensity were identified in multiple vascular territories in two patients, and microemboli persisted despite therapeutic anticoagulation in a third patient. Of the three patients without evidence of microemboli on TCD ultrasonography, two patients had suffered a confirmed ischemic stroke, while one remained with refractory encephalopathy. CONCLUSIONS: TCD ultrasonography for microemboli detection identified three patients with confirmed COVID-19 with evidence of cerebral arterial microemboli, including one who was therapeutically anticoagulated. TCD ultrasonography provides a non-invasive method for evaluating cerebral microemboli in patients with COVID-19 and may be useful in assessing response to treatment in cases with suspected or confirmed disorders of hypercoagulability. Further studies investigating the prevalence of cerebral microemboli and associated risk factors are needed to characterize their pathogenic mechanism and guide therapeutic interventions in hospitalized COVID-19 patients.

Patient Education in Neurosurgery: Part 1 of a Systematic Review.

BACKGROUND: Patient education has become increasingly important in neurosurgery. However, little is known regarding how to comprehensively educate neurosurgical patients. In the first part of a 2-part systematic review, we identify baseline patient understanding and educational needs, examine existing patient education materials, and characterize shortcomings in neurosurgical patient education practices. Our findings may guide neurosurgeons, departments, and professional associations in improving communication with patients. METHODS: A 2-part systematic review was conducted using the PubMed, Embase, and Scopus databases. Titles and abstracts were read and selected for full text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes. RESULTS: Of 1617 resultant articles, 41 were included. Patient comprehension was low. Patient informational needs differed across patients and between patients and neurosurgeons. Patient informational needs were often unmet, promoting dissatisfaction. Written educational materials from government agencies, professional associations, neurosurgery departments, neurosurgeons, or widely read Web sites were written at a reading level above the recommended reading level, with complex topics written at a higher level. Information found on hospital and university Web sites was poor quality because of self-marketing and lack of reference to peer-reviewed literature. Educational videos created by universities and hospitals were poor quality. CONCLUSIONS: Current in-clinic discussions and education materials show shortcomings, promoting poor comprehension. Neurosurgeons, departments, and professional organizations can act to improve the effectiveness of patient education initiatives. This policy will better inform patients, increase rapport between neurosurgeons and patients, and improve patient decision making and satisfaction.

Patient Education in Neurosurgery: Part 2 of a Systematic Review.

BACKGROUND: Increasing focus has been placed on patient education to optimize care. In the second part of a 2-part systematic review, we characterize the scope of interventions specifically created to improve neurosurgery patient education, assess the effectiveness of these interventions, and extract features of existing interventions that may be incorporated into future patient education interventions. Our findings may help promote the creation of effective, patient-centered educational interventions. METHODS: A 2-part systematic review was conducted using the PubMed, Embase, and Scopus databases. Titles and abstracts were read and selected for full text review. Studies meeting prespecified inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes. RESULTS: Of 1617 resultant articles, 33 were included. Print materials, electronic materials, models, and interventions using multiple modalities improved patient knowledge, decreased anxiety, and increased satisfaction. Electronic materials were preferred. Interventions using multiple modalities engaging multiple sensory systems were reported most beneficial. Video was rated the most effective medium for reinforcing spoken conversation between neurosurgeons and patients. Three-dimensional models decreased the time required for preoperative patient conversation but could be perceived as emotionally confronting. Virtual reality was preferred to patient models. CONCLUSIONS: Electronic interventions using multiple modalities in concert with each other may be most effective. Interventions should incorporate baseline knowledge and health literacy and address patient concerns and needs in a manner that is valid cross-contextually, uses clear communication, and is continuous. These interventions will improve the patient-friendliness of discussions with patients.

Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients.

OBJECTIVE: Covid-19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid-19. METHODS: We examined neurologic manifestations in 509 consecutive patients admitted with confirmed Covid-19 within a hospital network in Chicago, Illinois. We compared the severity of Covid-19 and outcomes in patients with and without neurologic manifestations. We also identified independent predictors of any neurologic manifestations, encephalopathy, and functional outcome using binary logistic regression. RESULTS: Neurologic manifestations were present at Covid-19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%). Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Severe respiratory disease requiring mechanical ventilation occurred in 134 patients (26.3%). Independent risk factors for developing any neurologic manifestation were severe Covid-19 (OR 4.02; 95% CI 2.04-8.89; P < 0.001) and younger age (OR 0.982; 95% CI 0.968-0.996; P = 0.014). Of all patients, 362 (71.1%) had a favorable functional outcome at discharge (modified Rankin Scale 0-2). However, encephalopathy was independently associated with worse functional outcome (OR 0.22; 95% CI 0.11-0.42; P < 0.001) and higher mortality within 30 days of hospitalization (35 [21.7%] vs. 11 [3.2%] patients; P < 0.001). INTERPRETATION: Neurologic manifestations occur in most hospitalized Covid-19 patients. Encephalopathy was associated with increased morbidity and mortality, independent of respiratory disease severity.

Spinal neurovascular complications with anterior thoracolumbar spine surgery: a systematic review and review of thoracolumbar vascular anatomy.

OBJECTIVE: Spinal cord infarction due to interruption of the spinal vascular supply during anterior thoracolumbar surgery is a rare but devastating complication. Here, the authors sought to summarize the data on this complication in terms of its incidence, risk factors, and operative considerations. They also sought to summarize the relevant spinal vascular anatomy. METHODS: They performed a systematic literature review of the PubMed, Scopus, and Embase databases to identify reports of spinal cord vascular injury related to anterior thoracolumbar spine procedures as well as operative adjuncts and considerations related to management of the segmental artery ligation during such anterior procedures. Titles and abstracts were screened, and studies meeting inclusion criteria were reviewed in full. RESULTS: Of 1200 articles identified on the initial screening, 16 met the inclusion criteria and consisted of 2 prospective cohort studies, 10 retrospective cohort studies, and 4 case reports. Four studies reported on the incidence of spinal cord ischemia with anterior thoracolumbar surgery, which ranged from 0% to 0.75%. Eight studies presented patient-level data for 13 cases of spinal cord ischemia after anterior thoracolumbar spine surgery. Proposed risk factors for vasculogenic spinal injury with anterior thoracolumbar surgery included hyperkyphosis, prior spinal deformity surgery, combined anterior-posterior procedures, left-sided approaches, operating on the concavity side of a scoliotic curve, and intra- or postoperative hypotension. In addition, eight studies analyzed operative considerations to reduce spinal cord ischemic complications in anterior thoracolumbar surgery, including intraoperative neuromonitoring and preoperative spinal angiography. CONCLUSIONS: While spinal cord infarction related to anterior thoracolumbar surgery is rare, it warrants proper consideration in the pre-, intra-, and postoperative periods. The spine surgeon must be aware of the relevant risk factors as well as the pre- and intraoperative adjuncts that can minimize these risks. Most importantly, an understanding of the relevant spinal vascular anatomy is critical to minimizing the risks associated with anterior thoracolumbar spine surgery.