Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Neurological Complications Associated with Hereditary Bleeding Disorders.

PURPOSE OF REVIEW: Hereditary bleeding disorders may have a wide variety of clinical presentations ranging from mild mucosal and joint bleeding to severe central nervous system (CNS) bleeding, of which intracranial hemorrhage (ICH) is the most dreaded complication. In this review, we will discuss the pathophysiology of specific hereditary bleeding disorders, namely, hemophilia A, hemophilia B, and von Willebrand disease (vWD); their clinical manifestations with a particular emphasis on neurological complications; a brief overview of management strategies pertaining to neurological complications; and a review of literature guiding treatment strategies. RECENT FINDINGS: ICH is the most significant cause of morbidity and mortality in patients with hemophilia. Adequate control of bleeding with the administration of specific factors or blood products, identification of risk factors for bleeding, and maintaining optimal coagulant activity are essential for appropriately managing CNS bleeding complications in these patients. The administration of specific recombinant factors is tailored to a patient's pharmacokinetics and steady-state levels. During acute bleeding episodes, initial factor activity should be maintained between 80 and 100%. Availability of monoclonal antibody Emicizumab has revolutionized prophylactic therapies in patients with hemophilia. Management of ICH in patients with vWD involves using plasma-derived factor concentrates, recombinant von Willebrand factor, and supportive antifibrinolytic agents individualized to the type and severity of vWD. Hemophilia and vWD are the most common hereditary bleeding disorders that can predispose patients to life-threatening CNS complications-intracranial bleeds, intraspinal bleeding, and peripheral nerve syndromes. Early care coordination with a hematologist can help develop an effective prophylactic regimen to avoid life-threatening bleeding complications in these patients. Further research is needed to evaluate using emicizumab as an on-demand treatment option for acute bleeding episodes in patients with hemophilia.

Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.

PURPOSE OF REVIEW: This review aims to provide an overview of neuroinflammation in ischemic and hemorrhagic stroke, including recent findings on the mechanisms and cellular players involved in the inflammatory response to brain injury. RECENT FINDINGS: Neuroinflammation is a crucial process following acute ischemic stroke (AIS) and hemorrhagic stroke (HS). In AIS, neuroinflammation is initiated within minutes of the ischemia onset and continues for several days. In HS, neuroinflammation is initiated by blood byproducts in the subarachnoid space and/or brain parenchyma. In both cases, neuroinflammation is characterized by the activation of resident immune cells, such as microglia and astrocytes, and infiltration of peripheral immune cells, leading to the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. These inflammatory mediators contribute to blood-brain barrier disruption, neuronal damage, and cerebral edema, promoting neuronal apoptosis and impairing neuroplasticity, ultimately exacerbating the neurologic deficit. However, neuroinflammation can also have beneficial effects by clearing cellular debris and promoting tissue repair. The role of neuroinflammation in AIS and ICH is complex and multifaceted, and further research is necessary to develop effective therapies that target this process. Intracerebral hemorrhage (ICH) will be the HS subtype addressed in this review. Neuroinflammation is a significant contributor to brain tissue damage following AIS and HS. Understanding the mechanisms and cellular players involved in neuroinflammation is essential for developing effective therapies to reduce secondary injury and improve stroke outcomes. Recent findings have provided new insights into the pathophysiology of neuroinflammation, highlighting the potential for targeting specific cytokines, chemokines, and glial cells as therapeutic strategies.

Vagus Nerve Stimulation in Ischemic Stroke.

PURPOSE OF REVIEW: Vagus nerve stimulation (VNS) has emerged as a potential therapeutic approach for neurological and psychiatric disorders. In recent years, there has been increasing interest in VNS for treating ischemic stroke. This review discusses the evidence supporting VNS as a treatment option for ischemic stroke and elucidates its underlying mechanisms. RECENT FINDINGS: Preclinical studies investigating VNS in stroke models have shown reduced infarct volumes and improved neurological deficits. Additionally, VNS has been found to reduce reperfusion injury. VNS may promote neuroprotection by reducing inflammation, enhancing cerebral blood flow, and modulating the release of neurotransmitters. Additionally, VNS may stimulate neuroplasticity, thereby facilitating post-stroke recovery. The Food and Drug Administration has approved invasive VNS (iVNS) combined with rehabilitation for ischemic stroke patients with moderate to severe upper limb deficits. However, iVNS is not feasible in acute stroke due to its time-sensitive nature. Non-invasive VNS (nVNS) may be an alternative approach for treating ischemic stroke. While the evidence from preclinical studies and clinical trials of nVNS is promising, the mechanisms through which VNS exerts its beneficial effects on ischemic stroke are still being elucidated. Therefore, further research is needed to better understand the efficacy and underlying mechanisms of nVNS in ischemic stroke. Moreover, large-scale randomized clinical trials are necessary to determine the optimal nVNS protocols, assess its long-term effects on stroke recovery and outcomes, and identify the potential benefits of combining nVNS with other rehabilitation strategies.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

PURPOSE OF REVIEW: Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. RECENT FINDINGS: Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Low dose intravenous cangrelor versus glycoprotein IIb/IIIa inhibitors in endovascular treatment of tandem lesions.

OBJECTIVES: Intravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelor versus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs). MATERIALS AND METHODS: We retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH), parenchymal hematoma type 1 and 2 (PH1-PH2), and hemorrhagic infarction type 1 and 2 (HI1-HI2). RESULTS: Sixty-three patients received IV APT during MT, 30 were in the cangrelor group, and 33 were in the GP-IIb/IIIa inhibitors group. There were no significant differences in the rates of sICH (3.3% vs. 12.1%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), HI1-HI2 (21.4% vs 42.4%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), and PH1-PH2 (17.9% vs. 12.1%, aOR=1.63, 95%CI 0.29-9.83, p=0.577) between both treatment groups. However, there was a trend toward reduced hemorrhage rates with cangrelor. Cangrelor was associated with increased odds of complete reperfusion (aOR=5.86; 95%CI 1.57-26.62;p=0.013). CONCLUSIONS: In this retrospective non-randomized cohort study, our findings suggest that low dose cangrelor has similar safety and increased rate of complete reperfusion compared to IV GP-IIb/IIIa inhibitors. Further prospective studies are warranted to confirm this association.

Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke associated with high morbidity and mortality that is considered a medical emergency, mainly managed with adequate blood pressure control and creating a favorable hemostatic condition. However, to date, none of the randomized clinical trials have led to an effective treatment for ICH. It is vital to better understand the mechanisms underlying brain injury to effectively decrease ICH-associated morbidity and mortality. It is well known that initial hematoma formation and its expansion have detrimental consequences. The literature has recently focused on other pathological processes, including oxidative stress, neuroinflammation, blood-brain barrier disruption, edema formation, and neurotoxicity, that constitute secondary brain injury. Since conventional management has failed to improve clinical outcomes significantly, various neuroprotective therapies are tested in preclinical and clinical settings. Unlike intravenous administration, intranasal insulin can reach a higher concentration in the cerebrospinal fluid without causing systemic side effects. Intranasal insulin delivery has been introduced as a novel neuroprotective agent for certain neurological diseases, including ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Since there is an overlap of mechanisms causing neuroinflammation in these neurological diseases and ICH, we believe that preclinical studies testing the role of intranasal insulin therapy in ICH are warranted.

The Neurological Manifestations of Post-Acute Sequelae of SARS-CoV-2 infection.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health challenge. This review aims to summarize the incidence, risk factors, possible pathophysiology, and proposed management of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC) or neuro-PASC based on the published literature. RECENT FINDINGS: The National Institutes of Health has noted that PASC is a multi-organ disorder ranging from mild symptoms to an incapacitating state that can last for weeks or longer following recovery from initial infection with SARS-CoV-2. Various pathophysiological mechanisms have been proposed as the culprit for the development of PASC. These include, but are not limited to, direct or indirect invasion of the virus into the brain, immune dysregulation, hormonal disturbances, elevated cytokine levels due to immune reaction leading to chronic inflammation, direct tissue damage to other organs, and persistent low-grade infection. A multidisciplinary approach for the treatment of neuro-PASC will be required to diagnose and address these symptoms. Tailored rehabilitation and novel cognitive therapy protocols are as important as pharmacological treatments to treat neuro-PASC effectively. With recognizing the growing numbers of COVID-19 patients suffering from neuro-PASC, there is an urgent need to identify affected individuals early to provide the most appropriate and efficient treatments. Awareness among the general population and health care professionals about PASC is rising, and more efforts are needed to understand and treat this new emerging challenge. In this review, we summarize the relevant scientific literature about neuro-PASC.

Peripheral Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: The present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Nerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.

Delayed Cerebral Ischemia after Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is the most feared complication of aneurysmal subarachnoid hemorrhage (aSAH). It increases the mortality and morbidity associated with aSAH. Previously, large cerebral artery vasospasm was thought to be the sole major contributing factor associated with increased risk of DCI. Recent literature has challenged this concept. We conducted a literature search using PUBMED as the prime source of articles discussing various other factors which may contribute to the development of DCI both in the presence or absence of large cerebral artery vasospasm. These factors include microvascular spasm, micro-thrombosis, cerebrovascular dysregulation, and cortical spreading depolarization. These factors collectively result in inflammation of brain parenchyma, which is thought to precipitate early brain injury and DCI. We conclude that diagnostic modalities need to be refined in order to diagnose DCI more efficiently in its early phase, and newer interventions need to be developed to prevent and treat this condition. These newer interventions are currently being studied in experimental models. However, their effectiveness on patients with aSAH is yet to be determined.

Glycemic Gap Predicts in-Hospital Mortality in Diabetic Patients with Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The relationship between admission hyperglycemia and intracerebral hemorrhage (ICH) outcome remains controversial. Glycemic gap (GG) is a superior indicator of glucose homeostatic response to physical stress compared to admission glucose levels. We aimed to evaluate the association between GG and in-hospital mortality in ICH. METHODS: We retrospectively identified consecutive patients hospitalized for spontaneous ICH at the 2 healthcare systems in the Twin Cities area, MN, between January 2008 and December 2017. Patients without glycosylated hemoglobin (HbA1c) test or those admitted beyond 24 hours post-ICH were excluded. Demographics, medical history, admission tests, and computed tomography data were recorded. GG was computed using admission glucose level minus HbA1c-derived average glucose. The association between GG and time to in-hospital mortality was evaluated by Cox regression analysis. Receiver operating characteristic (ROC) analysis with the DeLong test was used to evaluate the ability of GG to predict in-hospital death. RESULTS: Among 345 included subjects, 63 (25.7%) died during the hospital stay. Compared with survivors, non-survivors presented with a lower Glasgow coma scale score, larger hematoma volume, and higher white blood cells count, glucose, and GG levels at admission (p<0.001). GG remained an independent predictor of in-hospital mortality after adjusting for known ICH outcome predictors and potential confounders [adjusted hazard ratio: 1.09, 95% confidence interval (CI): 1.02-1.18, p = 0.018]. GG showed a good discriminative power (area under the ROC curve: 0.75, 95% CI: 0.68-0.82) in predicting in-hospital death and performed better than admission glucose levels in diabetic patients (p = 0.030 for DeLong test). CONCLUSIONS: Admission GG is associated with the risk of in-hospital mortality and can potentially represent a useful prognostic biomarker for ICH patients with diabetes.

Current Advances in Endovascular Treatment of Intracranial Atherosclerotic Disease and Future Prospective.

OBJECTIVES/BACKGROUND: Medical therapy is the first line of treatment for intracranial atherosclerotic disease (ICAD). Percutaneous transluminal angioplasty and stenting (PTAS) are mainly considered for those patients with severe stenosis and recurrent events despite aggressive medical therapy. In this review, we discuss the application of PTAS as a treatment option for ICAD and its future prospect. MATERIALS AND METHODS: We did the literature review of the key articles and guidelines to elaborate on the role of PTAS in the management of ICAD based on the current data and expert opinion. We searched PubMed, Google Scholar, and Scopus up to August 2020, and included articles published only in the English language. RESULTS: Since the publication of the results from SAMMPRIS and VISSIT trials, stenting is no longer recommended for secondary stroke prevention in patients with symptomatic ICAD. However, recent clinical studies on intracranial stenting for a subgroup of ICAD patients have shown promising results, likely due to better patient selection and continued advancement of endovascular techniques. CONCLUSION: There exists a lack of consensus regarding the best endovascular treatment approach (e.g., angioplasty alone or balloon mounted stent vs. self-expanding stent with or without prior angioplasty) or management of in-stent restenosis. Another area of clinical controversy relates to the ideal use and duration of antiplatelet therapy.

Correction to: Central Nervous System Manifestations Associated with COVID-19.

The original version contained incorrect formatting of Dr. Napolis. His first name should be Mario and his last name should be Di Napoli.

Central Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) has become a global health crisis of our time. The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization. COVID-19 has a wide range of respiratory symptoms from mild to severe and affects several other organs, increasing the complexity of the treatment. There is accumulating evidence to suggest that SARS-CoV-2 can target the nervous system. In this review, we provide an account of the COVID-19 central nervous system (CNS) manifestations. RECENT FINDINGS: A broad spectrum of the CNS manifestations including headache, impaired consciousness, delirium, loss of smell and taste, encephalitis, seizures, strokes, myelitis, acute disseminated encephalomyelitis, neurogenic respiratory failure, encephalopathy, silent hypoxemia, generalized myoclonus, neuroleptic malignant syndrome and Kawasaki syndrome has been reported in patients with COVID-19. CNS manifestations associated with COVID-19 should be considered in clinical practice. There is a need for modification of current protocols and standing orders to provide better care for COVID-19 patients presenting with neurological symptoms.

Transfemoral Approach to Induce Transient Middle Cerebral Artery Occlusion in Rats: The Use of Commercially Available Endovascular Wires.

BACKGROUND: Animal models of stroke play a crucial role in determining the pathophysiology of stroke progression and assessment of any new therapeutic approaches. Transient middle cerebral artery occlusion (tMCAo) in rodent models are the most common site-specific type of ischemia because of their relevance to the clinical setting. Compared with the intraluminal filament technique for inducing tMCAo, the transfemoral approach using endovascular wires is relatively a new technique METHODS: Here we present the use of commercially available wires used for neuro-endovascular surgical procedures to induce tMCAo in rats via a transfemoral approach. We used male Wistar rats in four groups to assess the effect of occlusion time (1 vs. 2 hours) and the wire type (PT2 TM 0.014″ vs. TransendTM EX, 0.014″, Boston Scientific, MA, USA). Infarct volume, edema, neurological deficits, and pro-inflammatory/anti-inflammatory blood biomarkers were used as outcome measures. RESULTS: We observed a significant effect of the wire type on the infarct volume (p value = 0.0096) where infarcts were slightly larger in the PT2 wiregroups. However, the occlusion time had no significant effect on infarct volume, even though the interaction between wire-type * occlusion-time was significant (p value = 0.024). Also, the amount of edema and blood pro-inflammatory/anti-inflammatory biomarkers were not statistically different among the wire-type and occlusion-time groups. CONCLUSIONS: The choice of appropriate endovascular wire should probably be the focus of the study design instead of the occlusion time when planning an experiment. The transfemoral approach using endovascular wires for inducing tMCAo in rats provides a more consistent outcome with fewer complications compared with suture filament models.

Exploration of Multiparameter Hematoma 3D Image Analysis for Predicting Outcome After Intracerebral Hemorrhage.

BACKGROUND: Rapid diagnosis and proper management of intracerebral hemorrhage (ICH) play a crucial role in the outcome. Prediction of the outcome with a high degree of accuracy based on admission data including imaging information can potentially influence clinical decision-making practice. METHODS: We conducted a retrospective multicenter study of consecutive ICH patients admitted between 2012-2017. Medical history, admission data, and initial head computed tomography (CT) scan were collected. CT scans were semiautomatically segmented for hematoma volume, hematoma density histograms, and sphericity index (SI). Discharge unfavorable outcomes were defined as death or severe disability (modified Rankin Scores 4-6). We compared (1) hematoma volume alone; (2) multiparameter imaging data including hematoma volume, location, density heterogeneity, SI, and midline shift; and (3) multiparameter imaging data with clinical information available on admission for ICH outcome prediction. Multivariate analysis and predictive modeling were used to determine the significance of hematoma characteristics on the outcome. RESULTS: We included 430 subjects in this analysis. Models using automated hematoma segmentation showed incremental predictive accuracies for in-hospital mortality using hematoma volume only: area under the curve (AUC): 0.85 [0.76-0.93], multiparameter imaging data (hematoma volume, location, CT density, SI, and midline shift): AUC: 0.91 [0.86-0.97], and multiparameter imaging data plus clinical information on admission (Glasgow Coma Scale (GCS) score and age): AUC: 0.94 [0.89-0.99]. Similarly, severe disability predictive accuracy varied from AUC: 0.84 [0.76-0.93] for volume-only model to AUC: 0.88 [0.80-0.95] for imaging data models and AUC: 0.92 [0.86-0.98] for imaging plus clinical predictors. CONCLUSIONS: Multiparameter models combining imaging and admission clinical data show high accuracy for predicting discharge unfavorable outcome after ICH.

The Magnitude of Blood Pressure Reduction Predicts Poor In-Hospital Outcome in Acute Intracerebral Hemorrhage.

BACKGROUND: Early systolic blood pressure (SBP) reduction is believed to improve outcome after spontaneous intracerebral hemorrhage (ICH), but there has been a limited assessment of SBP trajectories in individual patients. We aimed to determine the prognostic significance of SBP trajectories in ICH. METHODS: We collected routine data on spontaneous ICH patients from two healthcare systems over 10 years. Unsupervised functional principal components analysis (FPCA) was used to characterize SBP trajectories over first 24 h and their relationship to the primary outcome of unfavorable shift on modified Rankin scale (mRS) at hospital discharge, categorized as an ordinal trichotomous variable (mRS 0-2, 3-4, and 5-6 defined as good, poor, and severe, respectively). Ordinal logistic regression models adjusted for baseline SBP and ICH volume were used to determine the prognostic significance of SBP trajectories. RESULTS: The 757 patients included in the study were 65 ± 23 years old, 56% were men, with a median (IQR) Glasgow come scale of 14 (8). FPCA revealed that mean SBP over 24 h and SBP reduction within the first 6 h accounted for 76.8% of the variation in SBP trajectories. An increase in SBP reduction (per 10 mmHg) was significantly associated with unfavorable outcomes defined as mRS > 2 (adjusted-OR = 1.134; 95% CI 1.044-1.233, P = 0.003). Compared with SBP reduction < 20 mmHg, worse outcomes were observed for SBP reduction = 40-60 mmHg (adjusted-OR = 1.940, 95% CI 1.129-3.353, P = 0.017) and > 60 mmHg, (adjusted-OR = 1.965, 95% CI 1.011, 3.846, P = 0.047). Furthermore, the association of SBP reduction and outcome varied according to initial hematoma volume. Smaller SBP reduction was associated with good outcome (mRS 0-2) in small (< 7.42 mL) and medium-size (≥ 7.42 and < 30.47 mL) hematomas. Furthermore, while the likelihood of good outcome was low in those with large hematomas (≥ 30.47 mL), smaller SBP reduction was associated with decreasing probability of severe outcome (mRS 5-6). CONCLUSION: Our analyses suggest that in the first 6 h SBP reduction is significantly associated with the in-hospital outcome that varies with initial hematoma volume, and early SBP reduction > 40 mmHg may be harmful in ICH patients. For early SBP reduction to have an effective therapeutic effect, both target levels and optimum SBP reduction goals vis-à-vis hematoma volume should be considered.

Blood Pressure Variability: A New Predicting Factor for Clinical Outcomes of Intracerebral Hemorrhage.

Spontaneous primary intracerebral hemorrhage (ICH) is a stroke subtype associated with the highest mortality rate. High blood pressure (BP) is the most common cause of non-lobar ICH. Recent clinical trials have been inconclusive regarding the efficacy of aggressive BP lowering to improve ICH outcome. The association between high BP and ICH prognosis is rather complex and parameters other than absolute BP levels may be involved. In this regard, there is accruing evidence that BP variability (BPV) plays a major role in ICH outcome. Different BPV indices have been used to predict hematoma growth, neurological deterioration, and functional recovery. This review highlights the available evidence about the relationship between BPV and clinical outcomes among patients. We identified standard deviation (SD), residual SD, coefficient of variation, mean absolute change, average real variability, successive variation, spectral analysis using Fourier analysis, and functional successive variation (FSV) as indices to assess BPV. Most studies have demonstrated the association of BPV with ICH outcome, suggesting a need to monitor and control BP fluctuations in the routine clinical care of ICH patients. When large inter-subject variability exists, FSV is a viable alternative quantification of BPV as its computation is less sensitive to differences in the patient-specific observation schedules for BP than that of traditional indices.