Faculty Bibliography

OBJECTIVE/UNASSIGNED:A significant number of patients develop anxiety after stroke. The objective of this study was to identify risk factors for anxiety after hemorrhagic stroke that may facilitate diagnosis and treatment. METHODS/UNASSIGNED:Patients admitted between January 2015 and February 2021 with nontraumatic hemorrhagic stroke (intracerebral [ICH] or subarachnoid [SAH] hemorrhage) were assessed telephonically 3 and 12 months after stroke with the Quality of Life in Neurological Disorders Anxiety Short Form to evaluate the relationships between poststroke anxiety (T score >50) and preclinical social and neuropsychiatric history, systemic and neurological illness severity, and in-hospital complications. RESULTS/UNASSIGNED:Of 71 patients who completed the 3-month assessment, 28 (39%) had anxiety. There was a difference in Glasgow Coma Scale (GCS) scores on admission between patients with anxiety (median=14, interquartile range [IQR]=12-15) and those without anxiety (median=15, IQR=14-15) (p=0.034), and the incidence of anxiety was higher among patients with ICH (50%) than among those with SAH (20%) (p=0.021). Among patients with ICH, anxiety was associated with larger median ICH volume (25 cc [IQR=8-46] versus 8 cc [IQR=3-13], p=0.021) and higher median ICH score (2 [IQR=1-3] versus 1 [IQR=0-1], p=0.037). On multivariable analysis with GCS score, hemorrhage type, and neuropsychiatric history, only hemorrhage type remained significant (odds ratio=3.77, 95% CI=1.19-12.05, p=0.024). Of the 39 patients who completed the 12-month assessment, 12 (31%) had anxiety, and there was a difference in mean National Institutes of Health Stroke Scale scores between patients with (5 [IQR=3-12]) and without (2 [IQR=0-4]) anxiety (p=0.045). There was fair agreement (κ=0.38) between the presence of anxiety at 3 and 12 months. CONCLUSIONS/UNASSIGNED:Hemorrhage characteristics and factors assessed with neurological examination on admission are associated with the development of poststroke anxiety.

OBJECTIVE/UNASSIGNED:Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS/UNASSIGNED:The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS/UNASSIGNED:The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS/UNASSIGNED:Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.

BACKGROUND:The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS:We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS:Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS:More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.

Background: Headache is the most common neurological side effect of coronavirus disease 2019 (COVID-19) vaccination. However, the underlying reason for COVID-19 postvaccine headache has not been fully understood. In this study, we addressed the potential association of vaccine-related headaches with a history of allergy, atopic diseases, as well as other comorbid conditions to gain insight about the pathophysiology of this headache. Materials and Methods: This study analyzed the data from the Vaccine Adverse Event Reporting System database and reorganized dataset accordingly. The study included individuals aged 16-85 years who received the first or second dose of COVID-19 vaccines approved by the Food and Drug Administration. Allergy and atopic disease histories (reported food or drug allergy, allergic rhinitis, asthma, and other autoimmune diseases) and other accompanying diseases such as depression, anxiety, sleep disorders, fibromyalgia, and obesity of these subjects were examined from the revised data, and their relationship with COVID-19 vaccine-related headaches was investigated. Results: We found a statistically significant positive association in patients with a history of headache after COVID-19 vaccination and reported a history of allergy (P < 0.001). In the allergy subgroup (n = 14547 [37.1%]), the frequency of headaches following COVID-19 vaccine was found to be higher in those with drug, food, and/or multiple allergies (P < 0.05). A statistically significant relationship was disclosed between asthma, autoimmune diseases, and headache, but no association was found with allergic rhinitis (P < 0.001, P = 0.160). Furthermore, the rate of headaches after vaccination was found to be higher in people with fibromyalgia and depression (P < 0.001, both). Conclusion: Significant associations between headaches triggered by the COVID-19 vaccine and histories of allergy, fibromyalgia, and depression may suggest a shared predisposing mechanism for pathophysiology. Knowledge about allergy history and related comorbid conditions can be helpful in predicting COVID-19 vaccine headache. Future prospective data may provide further enlightenment on management.

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

INTRODUCTION/BACKGROUND:Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS:We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS:1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION/CONCLUSIONS:The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

BACKGROUND:Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19. METHODS:We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression. RESULTS:Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms). CONCLUSIONS:Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.