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.

Objective: To characterize neurologic manifestations in post‐hospitalization Neuro‐PASC (PNP) and non‐hospitalized Neuro‐PASC (NNP) patients.Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro‐COVID‐19 clinic between 5/2020 and 8/2021.Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre‐existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T‐score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro‐PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146–159

Objective: We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH). Methods: Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months. Results: We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate (p = 0.02), parsimoniously adjusted (p = 0.002), and fully adjusted models (p = 0.006), as well as greater hematoma growth (p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes (p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03–0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth. Conclusions: These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH.

Background and Objectives Although patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia. Methods We recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, and standardized cognitive assessments. Neuroglial scores (pGFAP/pNfL) were calculated to estimate the relative contribution of astroglial and neuronal involvement. Results We enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures. Discussion pNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.

Objective: To investigate neurologic manifestations of post‐acute sequelae of SARS‐CoV‐2 infection (Neuro‐PASC) in post‐hospitalization Neuro‐PASC (PNP) and non‐hospitalized Neuro‐PASC (NNP) patients across the adult lifespan.Methods: Cross‐sectional study of the first consecutive 200 PNP and 1,100 NNP patients evaluated at a Neuro‐coronavirus disease 2019 (COVID‐19) clinic between May 2020 and March 2023. Patients were divided into younger (18–44 years), middle‐age (45–64 years), and older (65+ years) age groups.Results: Younger and middle‐age individuals accounted for 142 of 200 (71%) of PNP and 995 of 1100 (90.5%) of NNP patients. Significant age‐related differences in the frequencies of comorbidities and abnormal neurologic findings demonstrated higher prevalence in older patients. Conversely, 10 months from COVID‐19 onset, we found significant age‐related differences in Neuro‐PASC symptoms indicating lower prevalence, and therefore, symptom burden, in older individuals. Moreover, there were significant age‐related differences in subjective impression of fatigue (median [interquartile range (IQR)] patient‐reported outcomes measurement information system [PROMIS] score: younger 64 [57–69], middle‐age 63 [57–68], older 60.5 [50.8–68.3]; p = 0.04) and sleep disturbance (median [IQR] PROMIS score: younger 57 [51–63], middle‐age 56 [53–63], older 54 [46.8–58]; p = 0.002) in the NNP group, commensurate with higher impairment in quality of life (QoL) among younger patients. Finally, there were significant age‐related differences in objective executive function (median [IQR] National Institutes of Health [NIH] toolbox score: younger 48 [35–63], middle‐age 49 [38–63], older 54.5 [45–66.3]; p = 0.01), and working memory (median [IQR] NIH toolbox score: younger 47 [40–53], middle‐age 50 [44–57], older 48 [43–58]; p = 0.0002) in NNP patients, with the worst performance coming from the younger group.Interpretation: Younger and middle‐age individuals are disproportionally affected by Neuro‐PASC regardless of acute COVID‐19 severity. Although older people more frequently have abnormal neurologic findings and comorbidities, younger and middle‐age patients suffer from a higher burden of Neuro‐PASC symptoms and cognitive dysfunction contributing to decreased QoL. Neuro‐PASC principally affects adults in their prime, contributing to profound public health and socioeconomic impacts warranting dedicated resources for prevention, diagnosis and interventions. ANN NEUROL 2025;97:369–383