2024 AHA/ASA Performance and Quality Measures for Spontaneous Intracerebral Hemorrhage: A Report From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released a revised spontaneous intracerebral hemorrhage guideline in 2022. A working group of stroke experts reviewed this guideline and identified a subset of recommendations that were deemed suitable for creating performance measures. These 15 performance measures encompass a wide spectrum of intracerebral hemorrhage patient care, from prehospital to posthospital settings, highlighting the importance of timely interventions. The measures also include 5 quality measures and address potential challenges in data collection, with the aim of future improvements.

Semiautomated Detection of Early Infarct Signs on Noncontrast CT Improves Interrater Agreement.

BACKGROUND: Acute ischemic infarct identification on noncontrast computed tomography (NCCT) is highly variable between raters. A semiautomated method for segmentation of acute ischemic lesions on NCCT may improve interrater reliability. METHODS: Patients with successful endovascular reperfusion from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) were included. We created relative NCCT (rNCCT) color-gradient overlays by comparing the density of a voxel on NCCT to the homologous region in the contralateral hemisphere. Regions with a relative hypodensity of at least 5% were visualized. We coregistered baseline and follow-up images. Two neuroradiologists and 6 nonradiologists segmented the acute ischemic lesion on the baseline scans with 2 methods: (1) manually outlining hypodense regions on the NCCT (unassisted segmentation) and (2) manually excluding areas deemed outside of the ischemic lesion on the rNCCT color map (rNCCT-assisted segmentation). Voxelwise interrater agreement was quantified using the Dice similarity coefficient and volumetric agreement between raters with the detection index (DI), defined as the true positive volume minus the false positive volume. RESULTS: From a total of 92, we included 61 patients. Median age was 59 (64-77), and 57% were female. Stroke onset was known in 39%. Onset to NCCT was median, 8.5 hours (7-11) and median 10 hours (8.4-11.5) in patients with known and unknown onset, respectively. Compared with unassisted NCCT segmentation, rNCCT-assisted segmentation increased the Dice similarity coefficient by >50% for neuroradiologists (Dice similarity coefficient, 0.38 versus 0.83; P<0.001) and nonradiologists (Dice similarity coefficient, 0.14 versus 0.84; P<0.001), and improved the DI among nonradiologists (mean improvement, 5.8 mL [95% CI, 3.1-8.5] mL, P<0.001) but not among neuroradiologists. CONCLUSIONS: The high variability of manual segmentations of the acute ischemic lesion on NCCT is greatly reduced using semiautomated rNCCT. The rNCCT map may therefore aid acute infarct detection and provide more reliable infarct estimates for clinicians with less experience.

Application of VirCapSeq-VERT and BacCapSeq in the diagnosis of presumed and definitive neuroinfectious diseases.

Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.

Time to Confirmed Neuroinfectious Diagnoses: Diagnostic Testing and Resource Allocation.

Background and Objectives: In a retrospective study evaluating the diagnostic approach of definitive neurological infections at a tertiary referral center, we assessed the time to diagnosis from presentation, number of diagnostic tests ordered, and modality of etiologic diagnosis. Methods: A total of 111 confirmed clinical cases of neurological infections from 2010-2018 were reviewed. Definitive neuroinfectious diagnoses were defined by positive cerebrospinal (CSF) polymerase chain reaction (PCR)/antigen, CSF culture, CSF antibody, serology, or pathology tests. Results: An etiologic diagnosis was determined at an average (SD) of 3.1 (5.9) days after presentation with an average (SD) of 27.7 (15.6) diagnostic tests ordered per workup.Viral neuro-infections were associated with lower intensive care unit (ICU) admission rates, shorter length of hospitalization, and fewer diagnostic tests ordered, as well as shorter time to definitive diagnosis (P < .05). Longer hospitalizations were associated with immunosuppression status regardless of infectious etiology (P < .001). Discussion: Given the high morbidity and mortality of neuroinfectious disease, specifically meningitis and encephalitis, efficient diagnostic testing is imperative to facilitate the most appropriate clinical course of action with special attention to the specific patient population.

Clinical Problem Solving: A 38-year-Old Woman With Systemic Lupus Erythematosus Presenting With Headache, Nausea, and Vomiting.

A 38-year-old woman with migraine headaches and systemic lupus erythematosus with recent cessation of her immunosuppressive therapy presents with prolonged headache and hypertensive emergency. Her examination is notable for a peripheral right facial palsy and stable malar rash. There are no signs of systemic infection nor systemic symptoms of a lupus flare. Initial CT head reveals bilateral hypodensities in the basal ganglia. Within 8 hours of presentation, she develops right hemiplegia and becomes encephalopathic. MRI shows multifocal acute infarcts (most notably in the left basal ganglia), enhancement of the right facial nerve, and multifocal vessel wall enhancement in the anterior and posterior circulation. We discuss the differential diagnosis, comprehensive workup, and subsequent treatment decisions in the management of this immunocompromised patient with encephalopathy, headache, and rapidly progressing focal neurologic deficits.

Leptomeningeal Disease Secondary to Thr60Ala Transthyretin Amyloidosis: Case Report and Review of the Literature.

A 31-year-old woman with transthyretin (TTR) amyloidosis secondary to a Thr60Ala mutation developed recurrent stroke-like episodes with fluctuating mental status. Evaluation for stroke and seizures was unrevealing. She was found to have leptomeningeal contrast enhancement on magnetic resonance imaging, which was confirmed to be CNS TTR amyloidosis on histopathology following brain and dura biopsy. While leptomeningeal disease has rarely been known to be associated with TTR amyloidosis, this is the first documented case of leptomeningeal disease secondary to a Thr60Ala mutation in the TTR gene. A literature review of TTR amyloidosis is presented with special focus on the treatment of leptomeningeal TTR amyloidosis.

Application of VirCapSeq-VERT and BacCapSeq In the Diagnosis of Presumed and Definitive Neuroinfectious Diseases.

Background: Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and complexity of bioinformatic analysis. Here we report the use of virus capture based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Design/Methods: Thirty-four samples were categorized: (1) Patients with definitive CNS infection by routine testing; (2) Patients meeting clinically Brighton Criteria (BC) for meningoencephalitis (3) Patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT and DNA extracts were used for BacCapSeq analysis. Results: Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3,11/26 samples (42%) were positive for at least one pathogen, however 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. Conclusions: HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess clinical value of this novel technique, clinicians should understand benefits and limitations of using this modality.

Uncontrolled HIV and inflammation is associated with intracranial saccular aneurysm presence.

OBJECTIVE: To study biomarkers of inflammation in cerebrovascular disease, exploring modifiable and non-modifiable biochemical and clinical risk factors associated with the presence of intracranial saccular aneurysms (ISAs) in an HIV-positive cohort. DESIGN: A cross-sectional community-based study was used to study blood biomarkers of inflammation as predictors of cerebrovascular disease, specifically the presence of ISAs in persons with HIV. Potential biochemical and clinical predictors of ISA presence were identified. METHODS: Time of flight magnetic resonance angiography and magnetic resonance imaging data identified the presence of ISAs in an HIV-positive cohort. Quantitative assays for neuroinflammatory biomarkers were performed on plasma blood samples. Lasso regression models were used to identify neuroinflammatory biomarkers and clinical risk factors associated with ISAs. RESULTS: Eight of 72 participants had radiographically identified ISAs. ISAs were more common in non-Hispanic black participants (18.5% vs. 0% presence in nonblack patients). Participants with well controlled HIV (defined as CD4+ count >200 cells/ml and undetectable viral load at time of magnetic resonance imaging) had lower odds of ISAs (odds ratio: 0.19, 95% confidence interval 0.05-0.79) independent of age, sex, ethnicity and vascular risk factors. Macrophage inflammatory protein-1 p, an HIV- suppressive factor detected in participant blood samples, was inversely associated with aneurysm presence. CONCLUSION: Well controlled HIV is associated with fewer ISAs. The identification of non-modifiable and modifiable risk factors contributing to ISA formation may provide valuable insight to impact clinical practice and inform the pathophysiology underlying ISA formation.

Allostatic load predicts racial disparities in intracerebral hemorrhage cognitive outcomes.

A large portion of stroke disparities remains unexplained, even after adjusting for demographic, comorbidity, and health care access variables. There is a critical need to close this knowledge gap by investigating novel factors that may contribute to stroke disparities. Allostatic load (AL) is the lifetime adverse physiologic impact of needing to adjust to socially structured stressors such as racism. AL has been shown to increase health vulnerability and worsen outcomes in marginalized populations. We sought to assess the differential impact of AL on cognitive outcomes post intracerebral hemorrhage (ICH) across race-ethnicity. The Intracerebral Hemorrhage Outcomes Project (ICHOP) prospectively collected data from patients presenting to Columbia Medical Center with ICH from 3/2009 to 5/2016. Data included demographics, stroke scores, labs, complications, neuroimaging, medical history, and discharge data. Five markers of AL (HbA1c, WBC, SBP, HR, ALB) were obtained. An AL score was generated by summing the elements in each patient that fell outside normal ranges, with AL score ranging 0-5. A linear regression model, adjusted for stroke severity and ICH volumes, was used to evaluate the relationship between AL and Modified Telephone Interview for Cognitive Status (TICS-m) at discharge, stratified by race-ethnicity. Among 248 white, 195 black, and 261 Hispanic ICH patients, neither mean AL nor mean TICS differed by race/ethnicity (p = 0.51, p = 0.79 respectively). In the overall cohort AL did not predict TICS at discharge (Beta -1.0, SE 1.1, p = 0.353). In Whites (beta 1.18, SE 2.5, p = 0.646) and Hispanics (beta -0.95, SE 1.6, p = 0.552) AL was not associated with TICS at discharge. In Black patients, higher AL was associated with a decrease in TICS at discharge (beta -3.2, SE 1.5, p = 0.049). AL is an important determinant of post ICH outcomes for certain minority populations. AL may explain some of the unexplained health disparities in stroke populations.

Determining an infectious or autoimmune etiology in encephalitis.

OBJECTIVES: Early presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are associated with IE or AE. METHODS: This was a multi-center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes. RESULTS: Three hundred and thirty-three individuals with confirmed acute meningoencephalitis were included. An infectious-nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p < 0.001), higher CSF white blood cell (WBC) (median 78 cells/µL, 8.00 cells/µL; p < 0.001), higher CSF protein (76.50 mg/dL, 40.90 mg/dL; p < 0.001), lower CSF glucose (58.00 mg/dL, 69.00 mg/dL; p < 0.001), lower serum WBC (7.80 cells/µL, 9.72 cells/µL; p < 0.050), higher erythrocyte sedimentation rate (19.50 mm/HR, 13.00 mm/HR; p < 0.05), higher C-reactive protein (6.40 mg/L, 1.25 mg/L; p = 0.005), and lack of antinuclear antibody titers (>1:40; NB 11.54%, AE 32.73%; p < 0.001). CSF-to-serum WBC ratio was significantly higher in NB compared to AE (NB 11.3, AE 0.99; p < 0.001). From these findings, the association of presenting with fever, CSF WBC ≥50 cells/µL, and CSF protein ≥75 mg/dL was explored in ruling-out AE. When all three criteria are present, an AE was found to be highly unlikely (sensitivity 92%, specificity 75%, negative predictive value 95%, and positive predictive value 64%). INTERPRETATIONS: Specific paraclinical data at initial presentation may risk stratify which patients have an IE versus AE.

Cerebrospinal Analysis in Patients With COVID-19.

BACKGROUND: Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care. METHODS: In this case series, we review patients diagnosed with SARS-CoV-2 undergoing lumbar puncture (LP) admitted to Columbia University Irving Medical Center (New York, NY, USA) from March 1 to May 26, 2020. In a subset of patients, CSF SARS-CoV-2 quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) testing is performed. RESULTS: The average age of 27 patients who underwent LP with definitive SARS-CoV-2 (SD) was 37.5 (28.7) years. CSF profiles showed elevated white blood cell counts and protein in 44% and 52% of patients, respectively. LP results impacted treatment decisions in 10 (37%) patients, either by change of antibiotics, influence in disposition decision, or by providing an alternative diagnosis. CSF SARS-CoV-2 qRT-PCR was performed on 8 (30%) patients, with negative results in all samples. CONCLUSIONS: Among patients diagnosed with SARS-CoV-2, CSF results changed treatment decisions or disposition in over one-third of our patient cohort. CSF was frequently abnormal, though CSF SARS-CoV-2 qRT-PCR was negative in all samples. Further studies are required to define whether CSF SARS-CoV-2 testing is warranted in certain clinical contexts.

Controlled cortical impact-induced neurodegeneration decreases after administration of the novel calpain-inhibitor Gabadur.

One aspect of secondary injury in traumatic brain injury is the marked increase in intracellular calcium and resultant over-activation of the calcium-dependent neutral cysteine protease calpain. Gabadur is a novel protease inhibitor with calpain-inhibition properties formulated from the classic protease inhibitor leupeptin linked to a pregabalin carrier. This construction allows the entire compound to cross the blood-brain barrier after peripheral administration to better target the site of injury. In this study, a single intraperitoneal dose of Gabadur was administered immediately following controlled cortical impact injury in rats. Neocortical slices were examined at 48 h post-injury via Fluoro-Jade B staining, revealing an improvement in cortical neurodegeneration in Gabadur treated rats. Levels of detrimental active calpain-2 measured via western blot were also decreased in rats receiving Gabadur. This data supports the benefit of targeted protease inhibition in the treatment of traumatic brain injury.

Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury.

Blunt impact produces a heterogeneous brain injury in people and in animal models of traumatic brain injury. We report that a single closed head impact to adult C57/BL6 mice produced two injury syndromes (CHI-1 and CHI-2). CHI-1 mice spontaneously reinitiated breathing after injury while CHI-2 mice had prolonged apnea and regained breathing only after cardiopulmonary resuscitation and supplementation of 100% O2. The CHI-1 group significantly regained righting reflex more rapidly than the CHI-2 group. At 7 days post-injury, CHI-1, but not CHI-2 mice, acquired but had no long-term retention of an active place avoidance task. The behavioral deficits of CHI-1 and CHI-2 mice were retained one-month after the injury. CHI-1 mice had loss of hippocampal neurons and localized white matter injury at one month after injury. CHI-2 had a larger loss of hippocampal neurons and more widespread loss of myelin and axons. High-speed videos made during the injury were followed by assessment of breathing and righting reflex. These videos show that CHI-2 mice experienced a larger vertical g-force than CHI-1 mice. Time to regain righting reflex in CHI-2 mice significantly correlated with vertical g-force. Thus, physiological responses occurring immediately after injury can be valuable surrogate markers of subsequent behavioral and histological deficits.