Unusual Post-COVID-19 Presentation With Tetraventricular Hydrocephalus: A Case Report.

Objective: COVID-19 infection is suggested as one of the causes for hydrocephalus (HCP) of unknown etiology. COVID-19 infection may present with a range of neurologic symptoms given viral neurotropic and neuroinvasive properties. Postinfectious HCP is a severe complication as a potential sequela of COVID-19 infection. Methods: We identified a patient with a history of recent COVID-19 infection who presented with chronic progressive headaches with nausea, vomiting, and blurry vision over 2 weeks. Results: Neurologic examination showed bilateral papilledema. The head CT scan showed tetraventricular enlargement and marked fourth ventricular dilation. Cine MRI showed fourth ventricular turbulent CSF flow. The patient underwent external ventricular drain placement and exploratory suboccipital craniotomy, which revealed a subarachnoid web that was microsurgically resected. Reconstituted CSF flow resolved the patient's symptoms and prevented complications. Discussion: Fourth ventricular outlet obstruction is a rare cause of tetraventricular HCP. In most cases, it is associated with a history of inflammatory conditions or hemorrhage. In our case, a history of recent COVID-19 infection and normal imaging before COVID-19 make COVID-19 the most probable explanation for HCP. We suggest considering COVID-19 infection in the differential diagnosis of HCP of unclear etiology.

Yield of ASPECTS and Collateral CTA Selection for Mechanical Thrombectomy within 6-24 hours from Symptom Onset in a Hub and Spoke System.

BACKGROUND: Recent extended window trials support the benefit of mechanical thrombectomy in anterior circulation large vessel occlusions with clinical-radiographic dissociation. Using trial imaging criteria, 6% were found eligible for MT in the EW in a hub-and-spoke system. We examined the eligibility and outcomes in consecutive extended window-mechanical thrombectomy patients using more pragmatic selection criteria. METHODS: We retrospectively analyzed single-institution data of anterior circulation large vessel occlusions patients presenting between 6-24 h who underwent mechanical thrombectomy based on a priori determined criteria including non-contrast CT head ASPECTS ≥ 6 and/or CTA collateral scores ASITN/SIR 2-4. Primary outcomes consisted of post-mechanical thrombectomy TICI 2b-3 and 3-month modified Rankin scores; safety outcomes consisted of in-hospital mortality and symptomatic intracerebral hemorrhage. RESULTS: 767 consecutive acute ischemic strokes patients presented within the 6-24 hour window, and of these 48 (6%) anterior circulation large vessel occlusions patients underwent mechanical thrombectomy. In this cohort the mean age was 63±17 years, 56% were male, the median NIHSS was 16 [IQR 10-19], the median ASPECTS was 9 (IQR 8-10), and 79% (n=38) had good CTA collaterals. Occlusions were primarily M1 MCA (46%), with 29% tandem occlusions. Successful recanalization (mTICI 2b or 3) was achieved in 73% (n=35), while 6% (n=3) of patients developed symptomatic intracerebral hemorrhage. In-hospital mortality was 25% (n=12) while 40% (n=19) achieved 3-month modified Rankin Scores 0-2. CONCLUSIONS: Our data suggest the use of pragmatic imaging approach of ASPECTS ≥6 with CTA collateral grade in extended time window which is already established in most hospitals.

Evaluation of the Safety of Rapid Administration of Undiluted High-Dose Intravenous Levetiracetam.

Background: Intravenous (IV) levetiracetam (LEV) is an antiseizure medication traditionally given as an intermittent infusion to mitigate potential adverse effects given its acidic formulation. The process of compounding may lead to delays in treating status epilepticus, which is why administration of undiluted doses is of interest. Prior studies have shown safety of IV doses from 1000 mg to 4500 mg; however, assessments of adverse side effects outside IV site reactions have not been studied. Methods: A retrospective analysis was completed with patients who received 1500 mg doses of undiluted IV LEV. We included patients ≥ 18 years old that received at least 1 dose of IV LEV 1500 mg from January 2018 to February 2021. Study end points included assessment of hemodynamic disturbance (bradycardia [HR less than 50 beats per minute] or hypotension [SBP less than 90 mmHg] within 1 hour or documented infusion reaction within 12 hours of LEV. Descriptive statistics were utilized. Results: A total 213 doses of 1500 mg of IV LEV were administered to 107 patients. Peripheral lines were used for 85.9% of doses. Approximately half of doses (57) were administered to patients on the general wards, with the remainder in the intensive care unit or emergency department. Two patients (1.9%) experienced bradycardia; however, 1 patient had pre-existing bradycardia. Three patients (3.8%) experienced hypotension; however, those patients were receiving vasopressors prior to the dose. There were no cases of infusion reaction. Conclusion: Undiluted, rapid administration of IV LEV 1500 mg was well tolerated and safe.

Complications of Mechanical Thrombectomy in Acute Ischemic Stroke.

Multiple randomized clinical trials have supported the use of mechanical thrombectomy (MT) as standard of care in the treatment of large vessel occlusion acute ischemic stroke. Optimal outcomes depend not only on early reperfusion therapy but also on post thrombectomy care. Early recognition of post MT complications including reperfusion hemorrhage, cerebral edema and large space occupying infarcts, and access site complications can guide early initiation of lifesaving therapies that can improve neurologic outcomes. Knowledge of common complications and their management is essential for stroke neurologists and critical care providers to ensure optimal outcomes. We present a review of the available literature evaluating the common complications in patients undergoing MT with emphasis on early recognition and management.

Admission Neutrophil to Lymphocyte Ratio for Predicting Outcome in Subarachnoid Hemorrhage.

PURPOSE: We sought to evaluate the relationship between admission neutrophil-to-lymphocyte ratio (NLR) and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. MATERIAL AND METHODS: Consecutive patients with aSAH were treated at two tertiary stroke centers during a five-year period. Functional outcome was defined as discharge modified Rankin score dichotomized at scores 0-2 (good) vs. 3-6 (poor). RESULTS: 474 aSAH patients were evaluated with a mean NLR 8.6 (SD 8.3). In multivariable logistic regression analysis, poor functional outcome was independently associated with higher NLR, older age, poorer clinical status on admission, prehospital statin use, and vasospasm. Increasing NLR analyzed as a continuous variable was independently associated with higher odds of poor functional outcome (OR 1.03, 95%CI 1.00-1.07, p=0.05) after adjustment for potential confounders. When dichotomized using ROC curve analysis, a threshold NLR value of greater than 6.48 was independently associated with higher odds of poor functional outcome (OR 1.71, 95%CI 1.07-2.74, p=0.03) after adjustment for potential confounders. CONCLUSIONS: Higher admission NLR is an independent predictor for poor functional outcome at discharge in aSAH patients. The evaluation of anti-inflammatory targets in the future may allow for improved functional outcome after aSAH.

Intravenous thrombolysis pretreatment and other predictors of infarct in a new previously unaffected territory (INT) in ELVO strokes treated with mechanical thrombectomy.

INTRODUCTION: One uncommon complication of mechanical thrombectomy (MT) is an infarct in a new previously unaffected territory (infarct in new territory (INT)). OBJECTIVE: To evaluate the predictors of INT with special focus on intravenous thrombolysis(IVT)pretreatmentbefore MT. METHODS: Consecutive patients with emergent large vessel occlusion (ELVO) treated with MT during a 5-year period were evaluated. INT was defined using standardized methodology proposed by ESCAPE investigators. The predictors of INT and its impact on outcomes were investigated. RESULTS: A total of 419 consecutive patients with ELVO received MT (mean age 64±15 years, 50% men, median baseline National Institutes of Health Stroke Scale score 16 points (IQR 11-20), 69% pretreated with IVT). The incidence of INT was lower in patients treated with combination therapy (IVTandMT) than in patients treated with MT alone, respectively (10% vs 20%; p=0.011). The INT group had more patients with posterior circulation occlusions than the group without INT (28% vs 10%, respectively; p<0.001). The rates of 3-month functional independence were lower in patients with INT (30% vs 50%; p=0.007). IVT pretreatment was not independently related to INT (OR=0.75; 95% CI 0.32 to 1.76), and INT did not emerge as an independent predictor of 3-month functional independence (OR=0.69; 95% CI 0.29 to 1.62) on multivariable logistic regression models. Location of posterior circulation occlusion was independently associated with a higher odds of INT (OR=3.33; 95% CI 1.43 to 7.69; p=0.005). CONCLUSIONS: IVT pretreatment is not independently associated with a lower likelihood of INT in patients with ELVO treated with MT. Patients with ELVO with posterior circulation occlusion are more likely to have INT after MT.

Impact of pretreatment with intravenous thrombolysis on reperfusion status in acute strokes treated with mechanical thrombectomy.

INTRODUCTION: We sought to evaluate the impact of pretreatment with intravenous thrombolysis (IVT) on the rate and speed of successful reperfusion (SR) in patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT) in a high-volume tertiary care stroke center. METHODS: Consecutive patients with ELVO treated with MT were evaluated. Outcomes were compared between patients who underwent combined IVT and MT (IVT+MT) and those treated with direct MT (dMT). The elapsed time between groin puncture to beginning of reperfusion (GPTBRT) and the numbers of device passes required to achieve SR were also documented. RESULTS: A total of 287 and 132 patients were treated with IVT+MT and dMT, respectively. The IVT+MT group had higher SR (73.8% vs 62.9%; p=0.023) and 3-month functional independence (modified Rankin Scale score 0-2;51.6% vs 38.2%; p=0.008) rates. The median GPTBRT was shorter in the IVT+MT group (48 (IQR 33-70) vs 70 (IQR 44-98) min; p<0.001). Among patients who achieved SR (n=292), the median number of required device passes was lower in the IVT+MT subgroup (1 (IQR 1-1) vs 2 (IQR 1-2); p<0.001), while the rate of patients requiring ≤2 device passes was higher (98% vs 77%; p<0.001). IVT+MT was independently related to higher odds of SR (OR 1.64; 95% CI 1.03 to 2.61; p=0.036) and shorter GPTBRT (unstandardized linear regression coefficient -20.39; 95% CI -27.56 to -13.22; p<0.001) on multivariable analyses adjusting for potential confounders. Among patients with SR, IVT+MT was independently associated with a higher likelihood of ≤2 device passes (OR 14.63; 95% CI 4.46 to 48.00; p<0.001). CONCLUSIONS: IVT pretreatment appears to increase the rates of SR and shortens the duration of the endovascular procedure by requiring fewer device passes in patients with ELVO treated with MT.

Mechanical thrombectomy outcomes in large vessel stroke with high international normalized ratio.

OBJECTIVE: Evaluating the safety and efficacy of mechanical thrombectomy (MT) in acute stroke patients due to emergent large vessel occlusion (ELVO) with high international-normalized-ratio (INR). METHODS: Consecutive ELVO patients treated with MT were evaluated from two centers. Outcome measures included symptomatic-intracranial-hemorrhage(sICH), three-month mortality, successful reperfusion(SR), and 3-month functional-independence(FI; mRS-scores of 0-2). Additionally, a meta-analysis of available cohort studies was performed to evaluate safety and efficacy of MT in ELVO patients with high INR. RESULTS: A total of 315 ELVO patients were evaluated. Of those 10 patients had INR >1.7 [mean age 63.5 ±â€¯15, median NIHSS-score: 17 points (IQR 14-22)],and remaining 305 ELVO patients had INR ≤ 1.7 ([mean age 62 ±â€¯14.4, median NIHSS-score: 17 points (IQR 12-21)]. Patients with high INR did not differ in terms of sICH (10.0% vs. 6.9%; p = .706), 3-month mortality (20.0% vs. 24.2%; p = .762), SR (88.9% vs. 69.4%; p = .209) and 3-month FI (50% vs. 49.3%; p = .762) compared to the rest. Meta-analysis of available studies (n = 5) showed that high INR was not related to sICH (OR: 0.94, 95%CI: 0.42-2.07; p = .88), 3-month mortality (OR: 1.07, 95%CI: CI 0.72-1.60; p = .73) and 3-month FI (OR: 0.69, 95%CI: 0.34-1.40; p = .30). CONCLUSIONS: MT can be performed safely and effectively in ELVO patients with high INR.

Endovascular Thrombectomy for Mild Strokes: How Low Should We Go?

Background and Purpose- Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) ≥6. However, EVT benefit for mild deficits large vessel occlusions (NIHSS, <6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with large vessel occlusion. Methods- A retrospective cohort of patients with anterior circulation large vessel occlusion and NIHSS <6 presenting within 24 hours from last seen normal were pooled. Patients were divided into 2 groups: EVT or medical management. Ninety-day mRS of 0 to 1 was the primary outcome, mRS of 0 to 2 was the secondary. Symptomatic intracerebral hemorrhage was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time last seen normal to presentation, center, IV alteplase, Alberta Stroke Program early computed tomographic score, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results- Two hundred fourteen patients (EVT, 124; medical management, 90) were included from 8 US and Spain centers between January 2012 and March 2017. The groups were similar in age, Alberta Stroke Program early computed tomographic score, IV alteplase rate and time last seen normal to presentation. There was no difference in mRS of 0 to 1 between EVT and medical management (55.7% versus 54.4%, respectively; adjusted odds ratio, 1.3; 95% CI, 0.64-2.64; P=0.47). Similar results were seen for mRS of 0 to 2 (63.3% EVT versus 67.8% medical management; adjusted odds ratio, 0.9; 95% CI, 0.43-1.88; P=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5% EVT, 48.4% medical management; odds ratio, 1.17; 95% CI, 0.54-2.52; P=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance ( P=0.07). Symptomatic intracerebral hemorrhage rates were higher with thrombectomy (5.8% EVT versus 0% medical management; P=0.02). Conclusions- Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS, <6) receiving thrombectomy irrespective of thrombus location, with increased symptomatic intracerebral hemorrhage rates, consistent with the guidelines recommending the treatment for NIHSS ≥6. There was a signal toward benefit with EVT only in M1 occlusions; however, this needs to be further evaluated in future randomized control trials.

Dual antiplatelet therapy pretreatment in IV thrombolysis for acute ischemic stroke.

OBJECTIVE: We sought to determine the safety and efficacy of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients with a history of dual antiplatelet therapy pretreatment (DAPP) in a prospective multicenter study. METHODS: We compared the following outcomes between DAPP+ and DAPP- IVT-treated patients before and after propensity score matching (PSM): symptomatic intracranial hemorrhage (sICH), asymptomatic intracranial hemorrhage, favorable functional outcome (modified Rankin Scale score 0-1), and 3-month mortality. RESULTS: Among 790 IVT patients, 58 (7%) were on DAPP before stroke (mean age 68 ± 13 years; 57% men; median NIH Stroke Scale score 8). DAPP+ patients were older with more risk factors compared to DAPP- patients. The rates of sICH were similar between groups (3.4% vs 3.2%). In multivariable analyses adjusting for potential confounders, DAPP was associated with higher odds of asymptomatic intracranial hemorrhage (odds ratio = 3.53, 95% confidence interval: 1.47-8.47; p = 0.005) but also with a higher likelihood of 3-month favorable functional outcome (odds ratio = 2.41, 95% confidence interval: 1.06-5.46; p = 0.035). After propensity score matching, 41 DAPP+ patients were matched to 82 DAPP- patients. The 2 groups did not differ in any of the baseline characteristics or safety and efficacy outcomes. CONCLUSIONS: DAPP is not associated with higher rates of sICH and 3-month mortality following IVT. DAPP should not be used as a reason to withhold IVT in otherwise eligible AIS candidates. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for IVT-treated patients with AIS, DAPP is not associated with a significantly higher risk of sICH. The study lacked the precision to exclude a potentially meaningful increase in sICH bleeding risk.

Therapeutic Benefit of Cilostazol in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized and Nonrandomized Studies.

OBJECTIVE: To assess the effectiveness of cilostazol, a selective inhibitor of phosphodiesterase type III, in preventing cerebral ischemia related to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of six clinical studies met the inclusion criteria and were included in the meta-analysis. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. The primary endpoint was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the final follow-up. RESULTS: A total of 136 (22%) of 618 subjects (38 and 98 assigned to cilostazol and control treatments, respectively) with SAH developed cerebral ischemia related to vasospasm. The risk of cerebral ischemia related to vasospasm was significantly lower in subjects assigned to cilostazol treatment (RR 0.43; 95% CI 0.31-0.60; p< 0.001). The risks of angiographic vasospasm (RR 0.67, 95% CI 0.54-0.84, p< 0.001 ) and new cerebral infarct (RR 0.37, 95% CI 0.24-0.57, p< 0.001) were significantly lower in subjects assigned to cilostazol treatment. There was a significantly lower rate of death or disability in subjects assigned to cilostazol treatment at follow-up (PR 0.55, 95% 0.39-0.78, p = 0.001). CONCLUSION: The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aneurysmal SAH in a large randomized clinical trial.

Antiplatelet pretreatment and outcomes following mechanical thrombectomy for emergent large vessel occlusion strokes.

BACKGROUND: Few data are available regarding the safety and efficacy of antiplatelet (APT) pretreatment in acute ischemic stroke (AIS) patients with emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy (MT). We sought to evaluate the association of APT pretreatment with safety and efficacy outcomes following MT for ELVO. METHODS: Consecutive ELVO patients treated with MT during a 4-year period in a tertiary stroke center were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), successful recanalization (SR; modified TICI score 2b/3), mortality, and functional independence (modified Rankin Scale scores of 0-2). RESULTS: The study population included 217 patients with ELVO (mean age 62±14 years, 50% men, median NIH Stroke Scale score 16). APT pretreatment was documented in 71 cases (33%). Patients with APT pretreatment had higher SR rates (77% vs 61%; P=0.013). The two groups did not differ in terms of sICH (6% vs 7%), 3-month mortality (25% vs 26%), and 3-month functional independence (50% vs 48%). Pretreatment with APT was independently associated with increased likelihood of SR (OR 2.18, 95% CI1.01 to 4.73; P=0.048) on multivariable logistic regression models adjusting for potential confounders. A significant interaction (P=0.014) of intravenous thrombolysis (IVT) pretreatment on the association of pre-hospital antiplatelet use with SR was detected. APT pretreatment was associated with SR (OR 2.74, 95% CI 1.15 to 6.54; P=0.024) in patients treated with combination therapy (IVT and MT) but not in those treated with direct MT (OR 1.78, 95% CI 0.63 to 5.03; P=0.276). CONCLUSION: APT pretreatment does not increase the risk of sICH and may independently improve the odds of SR in patients with ELVO treated with MT. The former association appears to be modified by IVT.

Cryptogenic Stroke and Significance of the Patent Foramen Ovale: A Case Series.

Stroke is the second leading cause of death globally and can lead to significant adverse outcomes in patients following the acute illness. Due to this high morbidity and mortality, adequate interventions can play a significant role in health outcomes. Patent foramen ovale is one of the major proposed causes of cryptogenic strokes and can be present in up to 25% of general population. In cryptogenic strokes, the relation of this structural heart defect is inversely proportional to age of patient. Here, we present three cases of cryptogenic strokes in patients with patent foramen ovale where it possibly plays a significant role. We demonstrate that in the younger age spectrum, patent foramen ovale plays a more significant role and treatment could prevent future stroke episodes.

Defining the localization and molecular characteristic of minor salivary gland label-retaining cells.

Adult stem cells (SCs) are important to maintain homeostasis of tissues including several mini-organs like hair follicles and sweat glands. However, the existence of stem cells in minor salivary glands (SGs) is largely unexplored. In vivo histone2B green fluorescent protein pulse chase strategy has allowed us to identify slow-cycling, label-retaining cells (LRCs) of minor SGs that preferentially localize in the basal layer of the lower excretory duct with a few in the acini. Engraftment of isolated SG LRC in vivo demonstrated their potential to differentiate into keratin 5 (basal layer marker) and keratin 8 (luminal layer marker)-positive structures. Transcriptional analysis revealed activation of TGFß1 target genes in SG LRC and BMP signaling in SG progenitors. We also provide evidence that minor SGSCs are sensitive to tobacco-derived tumor-inducing agent and give rise to tumors resembling low grade adenoma. Our data highlight for the first time the existence of minor SG LRCs with stem cells characteristic and emphasize the role of transforming growth factor beta (TGFß) pathway in their maintenance.