Pesticides and tremor: An overview of association, mechanisms and confounders.

Pesticides are a heterogeneous class of chemicals mainly used for the protection of crops from pests. Because of their very widespread use, acute or/and chronic exposure to these chemicals can lead to a plethora of sequelae inflicting diseases, many of which involve the nervous system. Tremor has been associated with pesticide exposure in human and animal studies. This review is aimed at assessing the studies currently available on the association between the various types of pesticides/insecticides and tremor, while also accounting for potential confounding factors. To our knowledge, this is the first coherent review on the subject. After appraising the available evidence, we call for more intensive research on this topic, as well as intonate the need of implementing future preventive measures to protect the exposed populations and to reduce potential disabilities and social drawbacks.

CTA-for-All: Impact of Emergency Computed Tomographic Angiography for All Patients With Stroke Presenting Within 24 Hours of Onset.

Background and Purpose- We sought to evaluate the impact of a Computed Tomographic Angiography (CTA) for All emergency stroke imaging protocol on outcome after large vessel occlusion (LVO). Methods- On July 1, 2017, the Henry Ford Health System implemented the policy of performing CTA and noncontrast computed tomography together as an initial imaging study for all patients with acute ischemic stroke (AIS) presenting within 24 hours of last known well, regardless of baseline National Institutes of Health Stroke Scale score. Previously, CTA was reserved for patients presenting within 6 hours with a National Institutes of Health Stroke Scale score ≥6. We compared treatment processes and outcomes between patients with AIS admitted 1 year before (n=388) and after (n=515) protocol implementation. Results- After protocol implementation, more AIS patients underwent CTA (91% versus 61%; P<0.001) and had CTA performed at the same time as the initial noncontrast computed tomography scan (78% versus 35%; P<0.001). Median time from emergency department arrival to CTA was also shorter (29 [interquartile range, 16-53] versus 43 [interquartile range, 29-112] minutes; P<0.001), more cases of LVO were detected (166 versus 96; 32% versus 25% of all AIS; P=0.014), and more mechanical thrombectomy procedures were performed (108 versus 68; 21% versus 18% of all AIS; P=0.196). Among LVO patients who presented within 6 hours of last known well, median time from last known well to mechanical thrombectomy was shorter (3.5 [interquartile range, 2.8-4.8] versus 4.1 [interquartile range, 3.3-5.6] hours; P=0.038), and more patients were discharged with a favorable outcome (Glasgow Outcome Scale 4-5, 53% versus 37%; P=0.029). The odds of having a favorable outcome after protocol implementation was not significant (odds ratio, 1.84 [95% CI, 0.98-3.45]; P=0.059) after controlling for age and baseline National Institutes of Health Stroke Scale score. Conclusions- Performing CTA and noncontrast computed tomography together as an initial assessment for all AIS patients presenting within 24 hours of last known well improved LVO detection, increased the mechanical thrombectomy treatment population, hastened intervention, and was associated with a trend toward improved outcome among LVO patients presenting within 6 hours of symptom onset.

The blood-brain barrier and beyond: Nano-based neuropharmacology and the role of extracellular matrix.

Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1) outline the state-of-the art knowledge on BBB passage, 2) address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3) highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nanosystem with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease.

Stroke after implantation of continuous flow left ventricular assist devices.

OBJECTIVE: Stroke remains a frequent and devastating complication after left ventricular assist device (LVAD) implantation, despite recent advances in device technology. The aim of this study was to analyze risk factors and outcomes of stroke following implantation of 200 continuous-flow LVADs at our institution. METHODS: We retrospectively analyzed patients who underwent LVAD implantation from 2011-2016. Data were available for a total of 200 patients. RESULTS: Post-LVAD stroke occurred in 13% of patients (26 of 200). Ischemic stroke occurred in 50% of patients (13 of 26), and hemorrhagic stroke in 50% (13 of 26). The median duration of LVAD support at the time of stroke was 257.4 days. Baseline characteristics did not differ significantly between the stroke and stroke-free cohorts. The mean international normalized ratio (INR) at the time of embolic stroke was 1.86 (range, 1.23-3.25) and 4.62 (range, 1.4-21.4) in patients with hemorrhagic stroke (P = .014). Mortality within 30 days of stroke was 31% (8 of 26). Mortality for hemorrhagic stroke was 63% (5 of 8) and 37% (3 of 8) for ischemic stroke ( P = .03). Among the 18 patients that survived stroke, 28% (5 of 18) received a heart transplant, 39% (7 of 18) are receiving ongoing LVAD support, and 33% (6 of 18) have died from unrelated causes. Multivariate analysis showed that INR level, aortic cross-clamping, a history of previous stroke, and postoperative infection were significant predictors for post-LVAD stroke. CONCLUSION: The occurrence of stroke significantly increases morbidity and mortality after LVAD implantation. Despite an adverse impact on survival and quality of life, several patients who suffered stroke still received a heart transplant. Furthermore, none of our patients had recurrence of a neurological event. Strict implementation of anticoagulation protocols is likely the mainstay of preventing this devastating complication.

Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA. We recorded baseline ICH volume, significant hematoma expansion (absolute [12.5 mL] or relative [>33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results- Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:-0.415 [95% CI, -0.780 to -0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22-0.85) in multivariable-adjusted models. Conclusions- Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.

Further evidence for a pain pathway involving the cingulate gyrus: a case of chronic cluster headache cured by glioblastoma.

The authors report a case of a 49-year-old man with long-standing, chronic cluster headache (CH) refractory to medical therapy and occipital nerve stimulation that resolved a few weeks prior to the diagnosis of glioblastoma involving primarily the right cingulate gyrus. An attempt to explore the underlying role of the cingulate cortex in pain modulation by appraising the current literature is presented. This report suggests that the cingulate gyri could be a potential target for neuromodulation in patients with medically refractory chronic CH.

Safety and outcomes in stroke mimics after intravenous tissue plasminogen activator administration: a single-center experience.

BACKGROUND: Patients with symptoms that impersonate a stroke but are later found to have an alternate diagnosis are termed stroke mimics. Stroke mimics treated with intravenous (IV) tissue plasminogen activator (t-PA) are exposed to hemorrhagic complications without benefit. The objective of this study is to describe the characteristics, safety, and outcomes of stroke mimic patients treated with t-PA within 4.5 hours. METHODS: All patients hospitalized after IV t-PA treatment at a tertiary care hospital and primary stroke center from January 2008 through December 2011 were reviewed. Stroke mimics were determined by review of clinical and imaging findings. Stroke mimics are described and compared with acute ischemic stroke patients for demographics, clinical characteristics, and bleeding complications. RESULTS: We identified 38 stroke mimic (12%) and 285 ischemic stroke (88%) t-PA-treated patients. Compared with ischemic stroke patients, mimic patients were younger, more often female, and reported a history of stroke more often. There were no differences in race, baseline stroke scale, or onset to treatment time. There were no intracerebral hemorrhages or deaths in the mimic patients but there were 2 systemic hemorrhages (5.2%). CONCLUSIONS: Treatment of mimic patients with IV t-PA appears to be safe in this cohort. Concern for intracerebral hemorrhage in mimic patients need not dissuade clinicians from administering t-PA when significant concern for ischemic etiology exists.

Clevidipine for acute hypertension in patients with subarachnoid hemorrhage: a pilot study.

PURPOSE: Clevidipine is a novel, ultra-short acting dihydropyridine. We hypothesized that clevidipine would rapidly control elevated blood pressure (BP) in patients with aneurysmal subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: This prospective open-label pilot study evaluated the efficacy and safety of clevidipine in reducing blood pressure (BP) to a pre-specified range and within 30 min before or after clipping or coiling of the aneurysm. RESULTS: We enrolled five patients who received eight clevidipine infusions, including 1587 systolic or diastolic BP data points. The mean SBP upper and lower goals were set at 154 and 122 mmHg. The primary end point of achieving SBP control within <30 min was reached in all patients within 14.2 ± 6.4 min at an infusion rate of 10.8 ± 9.1 mg/h. The mean pre-infusion, during infusion and post-infusion SBP measurements were 165.5 ± 2.55, 146.4 ± 2.48 and 159.3 ± 11.5 mmHg ( p < 0.05 for pre- vs infusion comparison), respectively. After reaching the primary end point and during the clevidipine infusion, 17.5% and 11.8% of SBP readings were above the upper and below the lower goals, respectively. No patients re-bled. In one patient, the infusion had to be stopped temporarily three times due to SBP decrease below the lower goal. CONCLUSION: Clevidipine controlled SBP in all patients with aneurysmal SAH in <22 min and kept it within the elective range 70% of the time without major complications.

Efficacy and Safety of Oral Factor XIa Inhibitors in Stroke Prevention: A Systematic Review and Meta-Analysis.

INTRODUCTION: Despite preventive measures, stroke rates remain high in the primary and secondary prevention settings. Factor XIa inhibition may offer a novel, safe and effective antithrombotic option for stroke prevention. METHODS: We conducted a systematic review and meta-analysis including all available randomized controlled clinical trials (RCTs) that investigated the efficacy and safety of factor XIa inhibitors versus controls in primary or secondary stroke prevention. The primary efficacy and safety outcomes of interest were symptomatic ischemic stroke (IS) and the composite of major bleeding and clinically relevant non-major bleeding. RESULTS: Four phase II dose-finding RCTs were included, comprising a total of 4732 patients treated with factor XIa inhibitors versus 1798 controls. Treatment with factor XIa inhibitors did not reduce the risk of IS compared to controls (RR: 0.89; 95% CI: 0.67-1.17). The composite of symptomatic IS and covert infarcts on brain MRI (RR: 1.01; 95% CI: 0.87-1.18), the composite of symptomatic IS and transient ischemic attack (TIA; RR: 0.78; 95% CI: 0.61-1.01), and the composite of major adverse cardiovascular events (RR: 1.07; 95% CI: 0.87-1.31) did not differ between the treatment groups. Treatment with factor XIa inhibitors did not increase the risk of the composite of major bleeding and clinically relevant non-major bleeding (RR: 1.19; 95% CI: 0.65-2.16), major bleeding alone (RR: 1.19; 95% CI: 0.64-2.22), intracranial bleeding (RR: 0.91; 95% CI: 0.26-3.19) or all-cause mortality (RR: 1.21; 95% CI: 0.77-1.90). CONCLUSION: This meta-analysis provides reassuring evidence regarding the safety of factor XIa inhibitors. These findings, coupled with potential signals of efficacy in reducing IS (and TIA), underscore the importance of ongoing phase III RCTs for providing definitive data regarding the effect of factor XIa inhibition on stroke prevention.

Lack of an association between SCFD1 rs10139154 polymorphism and amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Through a genome­wide association study (GWAS), the Sec1 family domain­containing protein 1 (SCFD1) rs10139154 variant at 14q12 has emerged as a risk factor gene for ALS. Moreover, it has been reported to influence the age at onset (AAO) of patients with ALS. The aim of the present study was to assess the association of the SCFD1 rs10139154 polymorphism with the risk of developing ALS. For this purpose, 155 patients with sporadic ALS and 155 healthy controls were genotyped for the SCFD1 rs10139154. The effect of the SCFD1 rs10139154 polymorphism was then examined on the following parameters: i) The risk of developing ALS; ii) the AAO of ALS; iii) the site of ALS onset (patients with bulbar onset ALS vs. healthy controls; and patients with limb onset ALS vs. healthy controls); and iv) the AAO of ALS onset with subgroup analyses based on the site of onset (bulbar and limb, crude and adjusted for sex). The analysis of all the outcomes was performed assuming five genetic models. Crude and adjusted analyses were applied. The threshold for statistical significance was set at 0.05. The results revealed no association between SCFD1 rs10139154 and any of the examined phenotypes in any of the models examined. On the whole, based on the findings of the present study, SCFD1 rs10139154 does not appear to play a determining role in the risk of developing ALS.

The Prognostic Value of Quantitative EEG in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

PURPOSE: Previous work has shown that quantitative EEG measures correlate with the severity of ischemic stroke. This has not been systematically validated in patients with acute ischemic stroke who have undergone mechanical thrombectomy. METHODS: Data were collected from 73 patients who underwent mechanical thrombectomy and had a standard head set EEG performed during their hospital admission. For each patient, the global delta-alpha ratio (DAR) and its difference between the two hemispheres were calculated. Associations between the global and interhemispheric DAR difference with the patients' National Institutes of Health Stroke and Modified Rankin Scale scores at discharge and 3 months after thrombectomy were assessed. RESULTS: The interhemispheric DAR difference correlated with the National Institutes of Health Stroke scores at discharge (Spearman R = 0.41, P = 0.0008), National Institutes of Health Stroke scores at 3 months (Spearman R = 0.60, P = 0.02) and Modified Rankin Scale scores at 3 months (Spearman R = 0.27, P = 0.01). In contrast, the global DAR did not correlate significantly with any of these clinical outcomes when evaluated as continuous variables. In a multivariate logistic regression model, both the interhemispheric DAR difference (ß = 0.25, P = 0.03) and the infarct volume (ß = 0.02, P = 0.03) were independently predictive of good versus poor functional outcome (Modified Rankin Scale score ≤2 vs. >2) at 3 months. CONCLUSIONS: The quantitative EEG measure of interhemispheric slow relative to fast frequencies power asymmetry correlated with the discharge and 3-month National Institutes of Health Stroke and Modified Rankin Scale scores and provided added value to infarct volume in predicting functional outcome at 3 months. These data support the prognostic value of quantitative EEG in ischemic stroke patients who have undergone mechanical thrombectomy.

High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete: Genetic Heterogeneity and Distinct Phenotypes.

Background and Objectives: Our goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece. Methods: We aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993-2019), were found to carry a pathogenic TTR variant. Results: Over the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18-37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54-78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants. Discussion: Our study revealed that the prevalence of hATTR in Crete is one of the world's highest. Three different pathogenic TTR variants causing distinct clinical phenotypes were identified in this relatively small population pool.

Moyamoya syndrome associated with Graves' disease: a case report and review of the literature.

We report a patient and critically review the literature in order to define the demographic, clinical, neuroradiologic, and treatment features of moyamoya syndrome (MMS) in the setting of Graves' disease (GD). We performed a comprehensive English language Medline search using the keywords "moyamoya," "Graves' disease," and "thyrotoxicosis." We included all patients with angiographic findings consistent with MMS. A 23-year-old woman with active GD presented with intermittent confusion and right arm paresis. Brain magnetic resonance imaging revealed acute left and chronic bilateral hemispheric infarcts. Cerebral angiography revealed multivessel intracranial occlusive disease. Initial treatment with plasmapheresis plus aspirin stabilized the patient's neurologic deficits. Antithyroid treatment plus subsequent surgical encephalomyosynangiosis resulted in prolonged neurologic stability. We studied 30 patients (27 women [90%], 23 of Asian descent [77%]), with a mean age of 29 ± 11.6 years. Hemiparesis (n = 12; 40%) was the leading clinical sign, and ischemic infarction was the most frequent neuroimaging finding (n = 26; 87%). Treatment regimens included antithyroid medications alone (n = 5; 17%), antithyroid plus antiplatelet agents (n = 9; 30%), neurosurgical revascularization after antithyroid medication (n = 11; 37%), and plasmapheresis in the acute thyrotoxic state (n = 2; 7%). Most patients had good short-to-medium term outcome (n = 14; 78% of reported outcome). Plasmapheresis-treated patients achieved neurologic stabilization and had good outcomes. MMS, an infrequent complication of GD, typically affects young women. Our findings indicate that plasmapheresis can stabilize the neurologic picture in the acute phase, and that antithyroid and antiplatelet therapy, combined with revascularization surgery, may improve long-term outcomes. Further work is needed to establish an optimal treatment strategy.

A Prospective, Observational, Cohort Study to Assess the Efficacy and Safety of Prolonged-Release Fampridine in Cognition, Fatigue, Depression, and Quality of Life in Multiple Sclerosis Patients: The FAMILY Study.

INTRODUCTION: The efficacy of prolonged-release fampridine (PR-FAM) may extend in multiple sclerosis (MS) beyond walking ability. The objective of this study was to evaluate the effect of PR-FAM treatment on cognition, fatigue, depression, and quality of life (QoL) in adult patients with MS in a real-world setting. METHODS: FAMILY was a multi-center, prospective, observational, real-world cohort study of MS patients receiving PR-FAM in the outpatient setting. Patients were treated as per PR-FAM's local prescribing information for 6 months. Standardized protocols and questionnaires were used to evaluate changes in cognition (PASAT; Paced Auditory Serial Addition Test), fatigue (MFIS; Modified Fatigue Impact Scale), depression (BDI-II; Beck Depression Inventory-II) and QoL (MusiQoL; MS International Quality-of-Life questionnaire, MSIS-29; Multiple Sclerosis Impact Scale: PHYS and PSYCH subscales) at 3 and 6 months compared to baseline. RESULTS: In total, 102 eligible patients from 8 sites in Greece were analysed, of whom 92 completed the study and 10 discontinued. At 6 months, PR-FAM treatment resulted in improvements from baseline in PASAT-3'' (p = 0.044), MFIS (p < 0.001), BDI-II (p < 0.001), MusiQoL (p < 0.001) and MSIS-29-PHYS (p = 0.012) and MSIS-PSYCH (p < 0.001). A positive effect was evident already at 3 months in PASAT-3'' (ns), MFIS (p = 0.020), BDI-II (p = 0.034), MusiQoL (p = 0.001), MSIS-29-PHYS (ns) and MSIS-29-PSYCH (p < 0.001). CONCLUSIONS: This observational study provides new data to the current literature in support of PR-FAM's positive effects in cognition, fatigue, depression, and QoL in a large, heterogeneous group of Greek MS patients in the real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03164018.

Genetic cause of epilepsy in a Greek cohort of children and young adults with heterogeneous epilepsy syndromes.

We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5 years, range 2-18 years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu AMT variant. A patient affected with Lafora disease carried the homozygous p.Arg171His EPM2A variant. A de novo heterozygous variant in the GABRG2 gene (p.Pro282Thr) was found in one patient and a pathogenic variant in the GRIN2B gene (p.Gly820Val) in another patient. Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter PDHX gene variant in one patient. In two additional epilepsy patients, the p.Ala1662Val and the novel non-sense p.Phe1330Ter SCN1A gene variants were found. Finally, in 3 patients we observed a novel heterozygous missense variant in SCN2A (p.Ala1874Thr), a heterozygous splice site variant in SLC2A1 (c.517-2A>G), as a cause of Glut1 deficiency syndrome, and a pathogenic variant in STXBP1 (p.Arg292Leu), respectively. In half of our cases (patients with variants in the GRIN2B, SCN1A, SCN2A and SLC2A1 genes), a genetic cause with potential management implications was identified.

Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach.

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

Nicardipine infusion for blood pressure control in patients with subarachnoid hemorrhage.

INTRODUCTION: To evaluate the efficacy, tolerability, and safety of nicardipine infusion in controlling the elevated blood pressure after subarachnoid hemorrhage (SAH). METHODS: Nicardipine infusion was initiated if the individual pre-specified systolic blood pressure (SBP) level goal, mandated by the admitting neurosurgeon, was not met. Systolic and diastolic BPs were measured on admission, hourly during the infusion and 12 h before and after the infusion. RESULTS: Twenty-eight patients with SAH required 50 nicardipine infusions in order to achieve a mean SBP goal of 152 mmHg. The 3,112 extracted BP measurements showed that mean infusion SBP was significantly lower than admission and pre-infusion SBP (mean 146.5 vs. 177.1 and 155.6 mmHg, P < 0.001, respectively) and significantly higher than post-infusion SBP (146.5 vs. 142.6 mmHg, P = 0.002). Five infusions were stopped prematurely, because of hypotension (n = 3), emergent surgery (n = 1), and failure to reach the SBP goal (n = 1). Rebleeding was not observed in any patient. Nicardipine achieved SBP control in 59.9% of hourly infusion measurements, with a trend for higher proportion of success with higher SBP goals. CONCLUSION: In this study, nicardipine infusion was a safe and moderately effective treatment for BP control in patients with SAH. Although SBP during nicardipine infusion was higher than the pre-specified goal in a significant percentage of hourly observations, this may be due to the drug administration protocol and other factors such as analgesia and sedation.

Patent Foramen Ovale in Cryptogenic Ischemic Stroke: Direct Cause, Risk Factor, or Incidental Finding?

Patent foramen ovale (PFO) has been associated with cryptogenic stroke. There is conflicting data and it remains uncertain whether PFO is the direct cause, a risk factor or an incidental finding. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signaling disruption. Main risk factors linked with PFO-attributable strokes are young age, PFO size, right-to-left shunt degree, PFO morphology, presence of atrial septal aneurysm, intrinsic coagulation-anticoagulation systems imbalance, and co-existence of other atrial abnormalities, such as right atrial septal pouch, Eustachian valve and Chiari's network. These may act independently or synergistically, multiplying the risk of embolic events. The RoPE score, a scale that includes factors such as young age, cortical infarct location and absence of traditional stroke risk factors, is associated with the probability of a PFO being pathogenic and stroke recurrence risk after the index stroke. Multiple investigators have attempted to correlate other PFO features with the risk of PFO-related stroke, but further investigation is needed before any robust conclusions are reached. PFO presence in young patients with cryptogenic stroke should be considered as etiologically suspect. Caution should be exercised in interpreting the relevance of other PFO features.