Stroke mechanisms in adult moyamoya disease: The association between infarction patterns and quantitative magnetic resonance angiography flow state.

INTRODUCTION: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. METHODS: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. RESULTS: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04). CONCLUSION: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.

Hypoperfusion Intensity Ratio is Associated with Stroke Mechanism in Patients Undergoing Mechanical Thrombectomy.

BACKGROUND: Hypoperfusion Intensity Ratio (HIR), defined as Tmax >10s/Tmax >6s on computed tomography perfusion (CTP), and stroke mechanisms have been independently correlated with angiographic collaterals and patient outcomes. Slowly developing atherosclerotic stenosis may foster collateral development, whereas cardioembolic occlusion may occur before collaterals mature. We hypothesized that favorable HIR is associated with large artery atherosclerosis (LAA) stroke mechanism and good clinical outcome. METHODS: Retrospective study of consecutive endovascularly-treated stroke patients with intracranial ICA or MCA M1/M2 occlusions, who underwent CTP before intervention, between January 2018 and August 2021. Patients were dichotomized into LAA+ or LAA- based on presence of LAA on angiography. HIR was dichotomized into favorable (HIR+) or unfavorable (HIR-) groups based on published thresholds. Good early outcome was defined as discharge mRS of 0-2. Bivariate and multivariable logistic regression were performed. RESULTS: 143 patients met inclusion. 21/143 were LAA+ (15%) and 65/143 (45%) were HIR+. HIR+ was significantly more frequent in LAA+ patients (67% vs. 42%, p= 0.035). Controlling for demographics, stroke severity, imaging findings, and medical comorbidities, LAA+ remained independently associated with HIR+ (OR 5.37 [95% CI 1.43 - 20.14]; p=0.013) as did smaller infarction core volume (<30 mL of CBF <30%: OR 7.92 [95% CI 2.27 - 27.64]; p = 0.001). HIR+ was not associated with good clinical outcome. CONCLUSIONS: Large artery atherosclerosis was independently associated with favorable HIR in patients undergoing mechanical thrombectomy. While favorable HIR was associated with smaller pre-treatment core infarcts, reflecting more robust collaterals, it was not associated with good clinical outcome.

Endovascular thrombectomy of large ischemic strokes: Reimagining the boundaries of reperfusion.

The cumulative results of the SELECT-2, ANGEL-ASPECTS, and RESCUE-JAPAN LIMIT clinical trials suggest that endovascular thrombectomy performed within 24 h of symptom onset, in patients presenting with large ischemic strokes, defined by parenchymal and/or perfusion imaging, is safe and is associated with better functional outcomes with a treatment effect that persisted across all subgroups of patients. Our aim was to review these studies and to discuss the implications that these studies may have on patient selection, systems of care, and the utility of our imaging modalities.

Mind + Machine: ChatGPT as a Basic Clinical Decisions Support Tool.

Background Generative artificial intelligence (AI) has integrated into various industries as it has demonstrated enormous potential in automating elaborate processes and enhancing complex decision-making. The ability of these chatbots to critically triage, diagnose, and manage complex medical conditions, remains unknown and requires further research. Objective This cross-sectional study sought to quantitatively analyze the appropriateness of ChatGPT (OpenAI, San Francisco, CA, US) in its ability to triage, synthesize differential diagnoses, and generate treatment plans for nine diverse but common clinical scenarios.  Methods Various common clinical scenarios were developed. Each was input into ChatGPT, and the chatbot was asked to develop diagnostic and treatment plans. Five practicing physicians independently scored ChatGPT's responses to the clinical scenarios.  Results  The average overall score for the triage ranking was 4.2 (SD 0.7). The lowest overall score was for the completeness of the differential diagnosis at 4.1 (0.5). The highest overall scores were seen with the accuracy of the differential diagnosis, initial treatment plan, and overall usefulness of the response (all with an average score of 4.4). Variance among physician scores ranged from 0.24 for accuracy of the differential diagnosis to 0.49 for appropriateness of triage ranking.  Discussion ChatGPT has the potential to augment clinical decision-making. More extensive research, however, is needed to ensure accuracy and appropriate recommendations are provided.

Ghost infarct core: A systematic review of the frequency, magnitude, and variables of CT perfusion overestimation.

BACKGROUND AND PURPOSE: CT perfusion (CTP) imaging is now widely used to select patients with large vessel occlusions for mechanical thrombectomy. Ghost infarct core (GIC) phenomenon has been coined to describe CTP core overestimation and has been investigated in several retrospective studies. Our aim is to review the frequency, magnitude, and variables associated with this phenomenon. METHODS: A primary literature search resulted in eight studies documenting median time from symptom onset to CTP, median estimated core size, median final infarct volume, median core overestimation of the GIC population, recanalization rates, good outcomes, and collateral status for this systematic review. RESULTS: All the studies investigated patients who underwent CTP within 6 hours of symptom onset, ranging from median times of 105 to 309 minutes. The frequency of core overestimation varied from 6% to 58.4%, while the median estimated ischemic core and final infarction volume ranged from 7 to 27 mL and 12 to 31 mL, respectively. The median core overestimation ranged from 3.6 to 30 mL with upper quartile ranges up to 58 mL. GIC was found to be a highly time-and-collateral-dependent process that increases in frequency and magnitude as the time from symptom onset to imaging decreases and in the presence of poor collaterals. CONCLUSIONS: CTP ischemic core overestimation appears to be a relatively common phenomenon that is most frequent in patients with poor collaterals imaged within the acute time window. Early perfusion imaging should be interpreted with caution to prevent the inadvertent exclusion of patients from highly effective reperfusion therapies.

Association between the degree of vertebrobasilar stenosis, location, infarction pattern, and QMRA flow state.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between the degree and location of vertebrobasilar stenosis and quantitative magnetic resonance angiography (QMRA) distal flow. METHODS: We retrospectively reviewed patients who presented with acute ischemic stroke with ≥50% stenosis of the extracranial or intracranial vertebral or basilar arteries, and QMRA performed within 1 year of stroke. Standardized techniques were used to measure stenosis and to dichotomize vertebrobasilar distal flow status. Patients were grouped based on the involved artery and the severity of disease. All p-values were calculated using chi-squared analysis and Fisher exact test with statistical significance defined as p < .05. RESULTS: Sixty-nine patients met study inclusion, consisting of 31 with low distal flow and 38 with normal distal flow. The presence of severe stenosis or occlusion was 100% sensitive, but only 47% predictive and 26% specific of a low distal flow state. Bilateral vertebral disease was only 55% sensitive but was 71% predictive and 82% specific of a low-flow state and was five times and nearly three times more likely to result in a low-flow state compared to unilateral vertebral disease (14%) and isolated basilar disease (28%), respectively. CONCLUSIONS: Severe stenosis of ≥70% may mark the minimal threshold required to cause hemodynamic insufficiency in the posterior circulation, but nearly half of these patients may remain hemodynamically sufficient. Bilateral vertebral stenosis resulted in a fivefold increase in QMRA low distal flow status compared to unilateral vertebral disease. These results may have implications in the design of future treatment trials of intracranial atherosclerotic disease.

Recurrent stroke risk in intracranial atherosclerotic disease.

Recurrent stroke risk secondary to intracranial atherosclerotic disease remains high despite aggressive medical treatment. This risk is further amplified in subgroups possessing biomarkers of hemodynamic insufficiency and potential for embolization, which have been shown to be independently and synergistically predictive of recurrent stroke. Luminal stenosis was predominantly used as entry criteria in major treatment trials, discounting the potential role of hemodynamics from primary analyses, limiting the strength of evidence and conclusions of these biomarkers to post-hoc analyses and other natural history studies. Future treatment trials should consider stratifying patients using a combination of these high-risk biomarkers. In the absence of trials, risk stratifying patients based on the presence of these markers may lend to more individualized clinical decisions. We aimed to summarize the studies that have investigated the relationship between biomarkers and their role in predicting recurrent stroke risk in intracranial atherosclerotic disease.

Subclavian steal phenomena in right-sided aortic arch with isolated left subclavian artery as demonstrated by quantitative-MRA.

Right-sided aortic arch with an isolated left subclavian artery is a very rare congenital anatomical variant that can lead to subclavian steal syndrome. We present a case of an asymptomatic patient who was incidentally found to have this variant on CT angiography with QMRA evidence of retrograde flow in the left vertebral artery consistent with subclavian steal phenomena. Since patients often remain asymptomatic until their compensatory mechanisms become compromised later in life, serial monitoring using non-invasive hemodynamic studies such as QMRA may guide treatment.

Case report: Bilateral globus pallidus lesions and delayed progressive leukoencephalopathy in COVID-19: Effects of hypoxia alone or combination of hypoxia and inflammation?

Background: The globus pallidus is a highly mitochondria-rich metabolic structure that is particularly sensitive to metabolic disturbances and hypoxia. Symmetric lesions of globus pallidus and delayed diffuse leukoencephalopathy were documented in toxic-metabolic disorders, hypoxia, a neurodegenerative disorder, and mitochondrial encephalopathies. Similar changes are also reported in individuals with active COVID-19 infections with associated hypoxia or critical illness. Case information: We describe a patient with post-COVID-19 infection who presented with rapid cognitive and neurological decline associated with similar neuroimaging structural changes but without toxic-metabolic changes or hypoxia. Despite multiple non-inflammatory cerebrospinal fluid studies, mechanisms involving post-COVID-19 inflammation and immune dysregulation are suspected, given the unexplained continued decline in the neurological status, lack of concurrent hypoxia or antecedent respiratory difficulties, and after a reasonable exclusion of alternative etiologies. Hypermetabolism of both anteromedial temporal structures and diffuse hypometabolism predominantly in the frontal region on PET scan provided indirect support for possible inflammatory mechanisms after reasonable exclusion of alternative etiologies, such as direct CNS infection, among others. The patient's neurological impairment improved substantially after treatment with pulse steroids, plasmapheresis, and rituximab. Conclusion: To the best of our knowledge, this is the first report of post-COVID-19 with bilateral symmetric contrast-enhancing necrotic lesions of globus pallidus with delayed diffuse supratentorial leukoencephalopathy with microhemorrhages without concurrent hypoxia or reported preceding symptoms suggestive of hypoxia. We suspect that these inflammatory mechanisms might be triggered by prior COVID-19 exposure/infection. Furthermore, the role of the cross-talk between inflammation and clinically mild or silent hypoxia linked to prior COVID-19 infection cannot be excluded. Awareness of these post-COVID-19 neurological sequelae and their potential pathophysiology among those with no known antecedent significant hypoxia are important for early recognition and treatment.

A Single-Health System Case Series of New-Onset CNS Inflammatory Disorders Temporally Associated With mRNA-Based SARS-CoV-2 Vaccines.

Background: Since 2020, over 250 million doses of mRNA-based SARS-CoV-2 vaccines have been administered in the United States and hundreds of millions worldwide between the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines. To date, there have been rare reports associating mRNA-based SARS-CoV-2 vaccines with episodes of inflammatory and autoimmune CNS disorders. We report a case series of five patients with new-onset neurological disorders of inflammatory or immunological origin temporally associated with these vaccines. Methods: A case-series of five patients within a single 23-hospital health system who developed new-onset CNS inflammatory disease within 2 weeks of receiving a dose of an mRNA-based SARS-CoV-2 vaccine. Results: Five cases of post-vaccination CNS disorders of immune origin (fatal ADEM; n = 1, new-onset NMOSD; n = 2, new-clinical onset MS-like syndrome but with preexisting clinically silent mild demyelination; n = 1, meningoencephalitis; n = 1) observed within 2 weeks of inoculation with either the first or second dose of mRNA-based SARS-CoV-2 vaccines (Moderna = 3, Pfizer = 2). Discussion: To our knowledge, these are among the emerging cases of CNS adverse events of immunological or inflammatory origin. These findings should be interpreted with great caution as they neither prove a mechanistic link nor imply a potential long-term increased risk in post-vaccination CNS autoimmunity. Larger prospective studies assessing the potential association between mRNA-based vaccination and the development of neurological adverse events of suspected immune origin, particularly among those with underlying CNS or systemic autoimmune disorders, are needed. The use of mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

Vertebrobasilar Stroke: Association Between Infarction Patterns and Quantitative Magnetic Resonance Angiography Flow State.

Background Treatment and prognosis of vertebrobasilar atherosclerotic disease differs depending on stroke mechanism, such as artery-to-artery embolism, branch atheromatous disease, and hemodynamic ischemia. Our aim was to investigate the relationship between infarction pattern and flow status using quantitative magnetic resonance angiography (QMRA), to determine the validity of using infarction patterns to infer stroke mechanism. Methods and Results This is a retrospective study of patients with ischemic stroke with intra- or extracranial vertebrobasilar atherosclerotic stenosis, who underwent magnetic resonance imaging of the brain, neurovascular imaging, and QMRA, between 2009 and 2021. Patients with cerebral infarction predating or following QMRA by ≥1 year, or QMRA studies performed for basilar thrombosis, vertebral dissection, or only postangioplasty/stenting, were excluded. Poststenotic flow (basilar and posterior cerebral arteries) was dichotomized as low-flow or normal-flow based on published criteria. Of 1211 consecutive patients who underwent QMRA noninvasive optimal analysis, 69 met inclusion. Mixed patterns were most common (46.4%), followed by perforator (23.2%), borderzone (14.5%), and territorial (15.9%). Patients with low-flow had a significantly higher rate of borderzone+ patterns (borderzone alone or in mixed pattern) compared with patients with normal-flow (77.4% low-flow versus 39.5% normal-flow, P=0.002). Borderzone+ patterns were associated with 61.5% probability of low-flow state, while no borderzone (perforator/territorial) patterns were associated with 76.7% probability of normal-flow state. Conclusions Borderzone infarction pattern (alone or mixed) was associated with low poststenotic posterior circulation flow by QMRA. However, borderzone pattern only moderately predicted low-flow state, and may be an unreliable flow marker. Therefore, infarct topography may complement, but should not replace hemodynamic studies to establish flow status.

EEG Abnormalities and Their Radiographic Correlates in a COVID-19 Inpatient Cohort.

Background and Objectives: To identify the prevalence of EEG abnormalities in patients with coronavirus disease 2019 (COVID-19) with neurologic changes, their associated neuroimaging abnormalities, and rates of mortality. Methods: A retrospective case series of 192 adult COVID-19-positive inpatients with EEG performed between March and June 2020 at 4 hospitals: 161 undergoing continuous, 24 routine, and 7 reduced montage EEG. Study indication, epilepsy history, intubation status, administration of sedatives or antiseizure medications (ASMs), metabolic abnormalities, neuroimaging pathology associated with epileptiform abnormalities, and in-hospital mortality were analyzed. Results: EEG indications included encephalopathy (54.7%), seizure (18.2%), coma (17.2%), focal deficit (5.2%), and abnormal movements (4.6%). Epileptiform abnormalities occurred in 39.6% of patients: focal intermittent epileptiform discharges in 25.0%, lateralized periodic discharges in 6.3%, and generalized periodic discharges in 19.3%. Seizures were recorded in 8 patients, 3 with status epilepticus. ASM administration, epilepsy history, and older age were associated with epileptiform abnormalities. Only 26.3% of patients presented with any epileptiform abnormality, 37.5% with electrographic seizures, and 25.7% patients with clinical seizures had known epilepsy. Background findings included generalized slowing (88.5%), focal slowing (15.6%), burst suppression (3.6%), attenuation (3.1%), and normal EEG (3.1%). Neuroimaging pathology was identified in 67.1% of patients with epileptiform abnormalities, over two-thirds acute. In-hospital mortality was 39.5% for patients with epileptiform abnormalities and 36.2% for those without. Risk factors for mortality were coma and ventilator support at time of EEG. Discussion: This article highlights the range of EEG abnormalities frequently associated with acute neuroimaging abnormalities in COVID-19. Mortality rates were high, particularly for patients in coma requiring mechanical ventilation. These findings may guide the prognosis and management of patients with COVID-19 and neurologic changes.

Axonal-Variant Guillian-Barre Syndrome Temporally Associated With mRNA-Based Moderna SARS-CoV-2 Vaccine.

We present a case of an 86-year-old woman who presented with a progressive quadriparesis two days after her second dose of Moderna SARS-CoV-2 vaccine, with cerebrospinal fluid (CSF) evidence of cytoalbuminocytological dissociation and electromyogram/nerve conduction studies (EMG/NCS) findings suggestive of acute axonal motor neuropathy. Her clinical symptoms did not improve with plasmapheresis. There appears to be a potential temporal association between the inoculation of mRNA-based SARS-CoV-2 vaccines and the development of Guillain-Barre Syndrome (GBS). Despite this possible association, infection prevention using highly effective mRNA-based vaccines remains highly recommended. Large epidemiological studies of SARS-CoV-2 vaccine-related adverse events are needed. Physicians should be aware of this possible temporal association since the prompt diagnosis and treatment of GBS can drastically improve outcomes. The aim is to report a case of axonal-variant GBS that was temporally associated with an mRNA-based SARS-CoV-2 vaccine.

Case Report: HSV-2 Encephalitis Presenting With Chorea; Effects of Infection Alone or Combination of Infection and Autoimmunity?

Background: Chorea as a symptom of late-onset post-infectious autoimmune encephalitis has been reported with HSV-1 but not HSV-2 encephalitis. Extrapyramidal symptoms are typically associated with the presence of anti-NMDA receptor antibodies but may also exist in antibody-negative individuals. Case: This case highlights a patient who presented with mental status changes and chorea as the initial manifestation of HSV-2 encephalitis. The choreiform movements failed to respond to antiviral medications but were rapidly responsive to plasmapheresis, which, together with abnormal intrathecal immunoglobulin synthesis, suggests a potential contribution of parainfectious immune-mediated process. The patient made a full recovery and a complete resolution of the chorea. Discussion: This is the first case associating HSV-2 encephalitis presentation with chorea. The neurological complications, including chorea, are largely related to active CNS HSV-2 infection, possibly together with triggered CNS autoimmunity despite undetectable CSF neuronal autoantibodies and normal neuroimaging. Early diagnosis and treatment with antiviral agent and immune therapies might be pivotal to optimize the clinical outcome.

Acute Seizures Occurring in Association With SARS-CoV-2.

Seizures are an infrequent and serious neurological complication of SARS-CoV-2 infection, with limited data describing the etiology and the clinical context in which these occur or the associated electrographic and imaging findings. This series details four cases of seizures occurring in patients with COVID-19 with distinct time points, underlying pathology, and proposed physiological mechanisms. An enhanced understanding of seizure manifestations in COVID-19 and their clinical course may allow for earlier detection and improved patient management.