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.

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.

Glioma lateralization: Focus on the anatomical localization and the distribution of molecular alterations (Review).

It is well known how the precise localization of glioblastoma multiforme (GBM) predicts the direction of tumor spread in the surrounding neuronal structures. The aim of the present review is to reveal the lateralization of GBM by evaluating the anatomical regions where it is frequently located as well as the main molecular alterations observed in different brain regions. According to the literature, the precise or most frequent lateralization of GBM has yet to be determined. However, it can be said that GBM is more frequently observed in the frontal lobe. Tractus and fascicles involved in GBM appear to be focused on the corticospinal tract, superior longitudinal I, II and III fascicles, arcuate fascicle long segment, frontal strait tract, and inferior fronto­occipital fasciculus. Considering the anatomical features of GBM and its brain involvement, it is logical that the main brain regions involved are the frontal­temporal­parietal­occipital lobes, respectively. Although tumor volumes are higher in the right hemisphere, it has been determined that the prognosis of patients diagnosed with cancer in the left hemisphere is worse, probably reflecting the anatomical distribution of some detrimental alterations such as TP53 mutations, PTEN loss, EGFR amplification, and MGMT promoter methylation. There are theories stating that the right hemisphere is less exposed to external influences in its development as it is responsible for the functions necessary for survival while tumors in the left hemisphere may be more aggressive. To shed light on specific anatomical and molecular features of GBM in different brain regions, the present review article is aimed at describing the main lateralization pathways as well as gene mutations or epigenetic modifications associated with the development of brain tumors.

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.

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.

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.

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.

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.

Factors defining occurrence of ischemic and hemorrhagic strokes during continuous flow left ventricular assist device support.

OBJECTIVE: LVAD-related strokes occur at a much higher rate compared to traditional open heart surgery. The pathophysiology of ischemic and hemorrhagic strokes after LVAD implantation is not well defined. The aim of this study was to better describe the etiopathogenesis of strokes during continuous flow LVAD support based on our institutional experience. METHODS: We performed a retrospective analysis of 200 patients, with and without stroke that underwent implantation of a continuous flow LVAD from 2011 to 2016. RESULTS: The incidences of stroke in our patient population were 13% (26/200), of which 50% (13/26) were ischemic and 50% hemorrhagic (13/26). Only 8% of strokes occurred within the first 48 h from LVAD implantation, all of which were ischemic. The median duration of support was 148 days for ischemic and 351 days (p = 0.012) for hemorrhagic strokes. The average mean arterial pressure measurements at the time of hospital discharge were 89 mmHg for patients who subsequently developed stroke and 72 mmHg (p = 0.03) for stroke-free patients. The average outpatient pressure measurements were 96 mmHg and 76 mmHg (p = 0.02) for the stroke and stroke-free patients, respectively. The mean velocity index showed the potential impairment of cerebral autoregulation. Multivariate analysis demonstrated that INR, COPD, aortic cross clamping, previous stroke, and device infections were statistically significant risk factors for stroke occurrence after LVAD implantation. CONCLUSIONS: In addition to LVAD-related thrombogenicity, the subsequent need for anticoagulation, and an acquired von Willebrand syndrome, several clinical factors, such as deviation from the anticoagulation regimen, hypertension, COPD, device infections, and aortic cross clamping, appear to have an influence on the extremely high rate of postoperative ischemic and hemorrhagic strokes.

Posterior Reversible Encephalopathy Syndrome, Multiple Sclerosis and interferon therapy: Association, co-incidence or convoluted interplay?

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) has only rarely been reported in patients with multiple sclerosis (MS). METHODS: Case report of a patient with relapsing remitting (RR) MS patient on interferon (INF) treatment, who developed posterior fossa PRES. RESULTS: A 46-year-old male diagnosed with RR MS in 2010 was placed on INF beta-1a therapy. He remained in clinical remission for seven years. He then presented with headache of one month duration and worsening upper extremity ataxia. Cranial MRI revealed two new enhancing cerebellar lesions (one with tumefactive features). Within the next 10 days the patient developed severe holocephalic headache, vomiting, altered consciousness and gait instability. Urgent brain MRI revealed diffuse hyperintense lesions in T2WI and FLAIR sequences in bilateral cerebellar hemispheres and the right thalamus, with marked swelling, increased diffusivity indicative of vasogenic edema and patchy-nodular enhancement, while smaller lesions were also found in posterior temporal, parietal and occipital lobes. Severely elevated blood pressure was noted. Treatment with hypertonic agents, esmolol drip and IV steroids was instituted, resulting in remarkable improvement within the next several days. Repeat MRI showed almost complete resolution of the cerebellar lesions. Interferon beta was discontinued and blood pressure remained well controlled. CONCLUSIONS: Patients with RR MS on IFN beta therapy can develop PRES via the combination of hypertension and endothelial dysfunction by IFN, even when stable on this treatment. Neurologists should be keen to differentiate the appearance of PRES lesions from those of fulminant MS relapse, opportunistic infections or malignancy.

Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System.

PURPOSE OF REVIEW: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic. RECENT FINDINGS: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2. SUMMARY: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS.

The role of MiRNA-21 in gliomas: Hope for a novel therapeutic intervention?

Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.

CYP1A2 rs762551 and ADORA2A rs5760423 Polymorphisms in Patients with Blepharospasm.

Blepharospasm (BSP) is a neurological movement disorder. Coffee consumption has been found to have a protective effect against BSP. BSP and apraxia of eyelid opening are particularly common among patients with PD. The CYP1A2 rs762551 and ADORA2A rs5760423 variants have been previously marginally associated with the risk of PD and are also implicated in caffeine metabolism pathways. The aim of the present study was to evaluate the effect of the CYP1A2 rs762551 and ADORA2A rs5760423 variants on BSP. A Southeastern European Caucasian (SEC) cohort of 206 BSP patients and 206 healthy controls was genotyped for rs762551 and rs5760423. CYP1A2 rs762551 was associated with a decreased BSP risk in the dominant (OR (95% CI) 0.62 (0.41-0.92), p = 0.017), log-additive (OR (95% CI) 0.68 (0.51-0.92), p = 0.011), and co-dominant modes (for the CC genotype OR (95% CI) 0.49 (0.25-0.93), p = 0.038). We provide preliminary evidence that CYP1A2 rs762551 is associated with BSP. Further studies and replication of our results are needed.

Intravenous thrombolysis in patients with chronic kidney disease: A systematic review and meta-analysis.

OBJECTIVE: To determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS). METHODS: A systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0-1), and 3-month functional independence (FI, mRS score 0-2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60-89 mL/min) to moderate (eGFR 30-59 mL/min) to severe (eGFR 15-29 mL/min). RESULTS: We identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19-1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01-1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18-1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72-2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47-0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46-0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01-1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27-3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01-1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09-1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70-0.92). CONCLUSIONS: After adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.

Does the CD33 rs3865444 Polymorphism Confer Susceptibility to Alzheimer's Disease?

Alzheimer's disease (AD) is a complex genetic disorder. To date, published data have reported conflicting results on the role of CD33 rs3865444 polymorphism in AD. The present study aimed at evaluating the effect of rs3865444 on AD in a large cohort of Greek native patients with AD. We also conducted a meta-analysis by pooling information from different studies on the same topic. Patients with AD (n = 327) and healthy controls (n = 327) were analyzed and genotyped for rs3865444. Single locus analyses were run to explore possible associations between CD33 rs3865444 polymorphism and AD. Our analysis yielded no significant interaction between AD and the CD33 rs3865444 polymorphism. The lack of interaction between the two variables persisted even after a pooled meta-analysis of 8 studies (with 13 datasets), with 4015 AD cases and 7981 controls. The overall results do not support the hypothesis that CD33 rs3865444 polymorphism increases the risk of AD. The results also suggest that the identification of functional variants in CD33 that are indisputably correlated with AD may be an important factor to investigate in future genetic screening studies.