Efficacy and safety of PCSK9 inhibitors for stroke prevention: Systematic review and meta-analysis.

OBJECTIVE: Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention. BACKGROUND: PCSK9i reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke. METHODS: We performed a systematic search of biomedical databases from inception to January 15, 2024, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by I2 and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-C and LpA reduction and stroke risk. RESULTS: Overall, 20 studies with 93,093 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low (I2 < 25 %). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-C levels by 11 % and LpA levels by 8 %. PCSK9i were associated with a significant reduction in stroke risk (RR 0.75, 95 % CI 0.66-0.86, I2 = 0 %), without an increase in mortality (RR 0.97, 95 % CI 0.87-1.08, I2 = 0 %). The risk of adverse neurological events was similar between groups (RR 0.99, 95 % CI 0.84-1.18, I2 = 11 %). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-C (LDL C ß = -0.01, 95 % CI = -0.03-0.02) and LpA (ß = -0.01, 95 % CI = -0.06-0.04) levels. CONCLUSIONS: PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-C- and LpA-independent mechanisms.

Efficacy and Safety of Mechanical Thrombectomy in Elderly and Non-Elderly Patients with Large Vessel Occlusion Stroke A Systematic Review and Meta-Analysis.

INTRODUCTION Mechanical thrombectomy (MT) is recommended for large vessel occlusion (LVO) stroke. However, most of the studies that investigated the superiority of MT over best medical management (BMM) alone included preponderantly non-elderly patients. Thus, there is uncertainty in relation to the efficacy of MT in the elderly. We aim to compare the effect of BMM to BMM plus (MT) among elderly and non-elderly patients with (LVO). METHODS We performed a systematic search of medical databases from inception to April 2023 to identify randomized studies that reported the functional outcome at 90 days by age for patients with LVO treated with MT vs. BMM. Patients were divided into elderly (>70 or >80 years, depending on the cut-off used in each study) and non-elderly. Outcomes were defined as excellent (modified Rankin Scale [mRS]≤1), good (mRS≤3), poor (mRS≥5), or death. Effect sizes were calculated by using random effects meta-analyses. Results were represented by odds ratio (OR) and their 95% confidence intervals (95% CI). RESULTS A total of 2,195 patients were included in the analysis (≥70 years, 7 trials, n= 696; ≥80 years, 2 trials, n=139). Non-elderly patients treated with MT had higher odds of excellent outcome (OR 3.05; 95% CI 2.23-4.18) and good outcome (OR 2.70; 95% CI 1.94-3.74), and lower odds of poor outcome (OR 0.54; 95% CI 0.40-0.72) and death (OR 0.63; 95% CI 0.41-0.96). Similarly, elderly patients treated with MT had higher odds of excellent (OR 2.39; 95% CI 1.05-5.45) and good outcomes (OR 2.18; 95% CI 1.43-3.33) and lower odds of poor outcome (OR 0.48; 95% CI 0.33-0.70) and mortality (OR 0.50; 0.26-0.95). When outcomes were analyzed by age subgroups, MT was associated with higher odds of good outcome in patients ≥70 years (OR 1.95, 95% CI 1.26-3.03) and ≥80 years (OR 4.43, 95% CI 1.02-19.23). DISCUSSION/CONCLUSION MT increases the likelihood of achieving a good outcome in elderly and non-elderly patients without increasing the risk of severe disability or death. MT, when otherwise clinically indicated, should be considered over BMM alone in both age groups.

Association of Unfavorable Social Determinants of Health With Stroke/Transient Ischemic Attack and Vascular Risk Factors in Hispanic/Latino Adults: Results From Hispanic Community Health Study/Study of Latinos.

BACKGROUND AND PURPOSE: Social determinants of health (SDOH) are non-medical factors that may contribute to the development of diseases, with a higher representation in underserved populations. Our objective is to determine the association of unfavorable SDOH with self-reported stroke/transient ischemic attack (TIA) and vascular risk factors (VRFs) among Hispanic/Latino adults living in the US. METHODS: We used cross-sectional data from the Hispanic Community Health Study/Study of Latinos. SDOH and VRFs were assessed using questionnaires and validated scales and measurements. We investigated the association between the SDOH (individually and as count: ≤1, 2, 3, 4, or ≥5 SDOH), VRFs and stroke/TIA using regression analyses. RESULTS: For individuals with stroke/TIA (n=388), the mean age (58.9 years) differed from those without stroke/TIA (n=11,210; 46.8 years; P<0.0001). In bivariate analysis, income <$20,000, education less than high school, no health insurance, perceived discrimination, not currently employed, upper tertile for chronic stress, and lower tertiles for social support and language- and social-based acculturation were associated with stroke/TIA and retained further. A higher number of SDOH was directly associated with all individual VRFs investigated, except for at-risk alcohol, and with number of VRFs (ß=0.11, 95% confidence interval [CI]=0.09-0.14). In the fully adjusted model, income, discrimination, social support, chronic stress, and employment status were individually associated with stroke/TIA; the odds of stroke/TIA were 2.3 times higher in individuals with 3 SDOH (95% CI 1.6-3.2) and 2.7 times (95% CI 1.9-3.7) for those with ≥5 versus ≤1 SDOH. CONCLUSION: Among Hispanic/Latino adults, a higher number of SDOH is associated with increased odds for stroke/TIA and VRFs. The association remained significant after adjustment for VRFs, suggesting involvement of non-vascular mechanisms.

Household income is associated with functional outcomes in a multi-institutional cohort of patients with ischemic stroke and COVID-19.

OBJECTIVES: The COVID-19 pandemic has heightened awareness of health disparities associated with socioeconomic status (SES) across the United States. We examined whether household income is associated with functional outcomes after stroke and COVID-19. MATERIALS AND METHODS: This was a multi-institutional, retrospective cohort study of consecutively hospitalized patients with SARS-CoV-2 and radiographically confirmed stroke presenting from March through November 2020 to any of five comprehensive stroke centers in metropolitan Chicago, Illinois, USA. Zip-code-derived household income was dichotomized at the Chicago median. Logistic regression was used to examine the relationship between household income and good functional outcome (modified Rankin Scale 0-3 at discharge, after ischemic stroke). RESULTS: Across five hospitals, 159 patients were included. Black patients comprised 48.1%, White patients 38.6%, and Hispanic patients 27.7%. Median household income was $46,938 [IQR: $32,460-63,219]. Ischemic stroke occurred in 115 (72.3%) patients (median NIHSS 7, IQR: 0.5-18.5) and hemorrhagic stroke in 37 (23.7%). When controlling for age, sex, severe COVID-19, and NIHSS, patients with ischemic stroke and household income above the Chicago median were more likely to have a good functional outcome at discharge (OR 7.53, 95% CI 1.61 - 45.73; P=0.016). Race/ethnicity were not included in final adjusted models given collinearity with income. CONCLUSIONS: In this multi-institutional study of hospitalized patients with stroke, those residing in higher SES zip codes were more likely to have better functional outcomes, despite controlling for stroke severity and COVID-19 severity. This suggests that area-based SES factors may play a role in outcomes from stroke and COVID-19.

Neuroimaging Markers for Determining Former American Football Players at Risk for Alzheimer's Disease.

NFL players, by virtue of their exposure to traumatic brain injury (TBI), are at higher risk of developing dementia and Alzheimer's disease (AD) than the general population. Early recognition and intervention before the onset of clinical symptoms could potentially avert/delay the long-term consequences of these diseases. Given that AD is thought to have a long pre-clinical incubation period, the aim of the current research was to determine whether former NFL players show evidence of incipient dementia in their structural imaging before diagnosis of AD. To identify neuroimaging markers of AD, against which former NFL players would be compared, we conducted a whole-brain volumetric analysis using a cohort of AD patients (ADNI clinical database) to produce a set of brain regions demonstrating sensitivity to early AD pathology (i.e., the "AD fingerprint"). A group of 46 former NFL players' brain magnetic resonance images were then interrogated using the AD fingerprint, that is, the former NFL subjects were compared volumetrically to AD patients using a T1-weighted magnetization-prepared rapid gradient echo sequence. The FreeSurfer image analysis suite (version 6.0) was used to obtain volumetric and cortical thickness data. The Automated Neuropsychological Assessment Metric-Version 4 was used to assess current cognitive functioning. A total of 55 brain regions demonstrated significant atrophy or ex vacuo dilatation bilaterally in AD patients versus controls. Of the 46 former NFL players, 41% demonstrated a greater than expected number of atrophied/dilated AD regions compared with age-matched controls, presumably reflecting AD pathology.

Association of Mediterranean Diet With Cognitive Decline Among Diverse Hispanic or Latino Adults From the Hispanic Community Health Study/Study of Latinos.

Importance: The Mediterranean diet may reduce the burden of Alzheimer disease and other associated dementias in Hispanic or Latino people. Objective: To investigate the association of a Mediterranean diet with cognitive performance among community-dwelling Hispanic or Latino adults. Design, Setting, and Participants: This cohort study analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), an HCHS/SOL ancillary study. Cognition tests were administered in the HCHS/SOL from March 2008 to June 2011 (visit 1) and in the SOL-INCA from October 2015 to March 2018 (visit 2). Participants included in the present study had completed a diet assessment at visit 1 and neurocognitive evaluations at visits 1 and 2. Data were analyzed from September 2021 to May 2022. Exposures: Mediterranean diet adherence was ascertained using the Mediterranean diet score (MDS) and was categorized as low (MDS: 0-4 points), moderate (MDS: 5-6 points), or high (MDS: 7-9 points). The mean of two 24-hour dietary recalls was used to calculate the MDS. Main Outcomes and Measures: Cognitive change between visits 1 and 2 was calculated by subtracting the cognitive score at visit 2 from the cognitive score at visit 1 and adjusting by the time elapsed between visits and cognitive score at visit 1. Neurocognitive tests administered were Brief Spanish-English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, word fluency, and Digit Symbol Substitution Test (DSST). Results of each test were z score-transformed and the means were averaged to create a global cognition score. Complex sample linear regression analysis was used to ascertain the association between MDS and neurocognitive performance at each visit and neurocognitive change. Results: A total of 6321 participants (mean [SE] age, 56.1 [0.18] years at visit 1; n = 4077 women [57.8%]) were included. Mediterranean diet adherence weighted frequencies were 35.8% (n = 2112 of 6321) for the low adherence group, 45.4% (n = 2795) for the moderate adherence group, and 18.8% (n = 1414) for the high adherence group. In the fully adjusted model, z score-transformed cognitive scores at visit 1 in the high vs low adherence groups were higher for B-SEVLT Sum (ß = 0.11; 95% CI, 0.02-0.20), B-SEVLT Recall (ß = 0.16; 95% CI, 0.07-0.25), and global cognition (ß = 0.10; 95% CI, 0.04-0.16) tests. In the mean follow-up time of 7 years, cognitive change in the high vs low adherence groups was less pronounced for B-SEVLT Sum (ß = 0.12; 95% CI, 0.05-0.20) and B-SEVLT Recall (ß = 0.14; 95% CI, 0.05-0.23), but not for word fluency, DSST score, or global cognition score. Conclusions and Relevance: Results of this cohort study suggested that high adherence to a Mediterranean diet was associated with better cognitive performance and decreased 7-year learning and memory decline among middle-aged and older Hispanic or Latino adults. Culturally tailored Mediterranean diet may reduce the risk of cognitive decline and Alzheimer disease in this population.

Neurological Manifestations of Myocarditis.

PURPOSE OF REVIEW: The present review discusses the neurological complications associated with myocarditis of different etiologies. RECENT FINDINGS: Myocarditis can be idiopathic or caused by different conditions, including toxins, infections, or inflammatory diseases. Clinical findings are variable and range from mild self-limited shortness of breath or chest pain to hemodynamic instability which may result in cardiogenic shock and death. Several neurologic manifestations can be seen in association with myocarditis. Tissue remodeling, fibrosis, and myocyte dysfunction can result in heart failure and arrhythmias leading to intracardiac thrombus formation and cardioembolism. In addition, peripheral neuropathies, status epilepticus, or myasthenia gravis have been reported in association with specific types of myocarditis. Multiple studies suggest the increasing risk of neurologic complications in patients with myocarditis. Neurologists should maintain a high suspicion of myocarditis in cases presenting with both cardiovascular and neurological dysfunction without a clear etiology.

Mechanical Thrombectomy vs Bridging Therapy for Anterior Circulation Large Vessel Occlusion Stroke: Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Current guidelines recommend the use of mechanical thrombectomy (MT) plus IV thrombolysis (aka bridging therapy [BT]) for patients with anterior circulation large vessel occlusion (LVO) stroke. However, clinical equipoise exists in relation to the use of BT vs MT alone. Our objective is to compare the efficacy and safety of BT and MT for anterior circulation LVO. METHODS: A systematic search of biomedical literature databases was performed from inception to October 29, 2021, to identify prospective and retrospective studies comparing the rates for functional independence (modified Rankin Scale score 0-2) and mortality at 90 days, symptomatic intracranial hemorrhage (sICH), and successful recanalization rates for MT and BT. Effect size was represented by odds ratio (OR), and analysis was done with random-effects meta-analysis. Heterogeneity was assessed by I 2 and Cochrane Q statistics. RESULTS: Overall, 41 studies with 14,885 patients were included. Mean ± SD age was 69 ± 11 years for BT and 70 ± 11 years for MT. All studies used alteplase as the thrombolytic agent. The BT group had 29% higher odds for functional independence (OR 1.29, 95% CI 1.16-1.44, I 2 = 42%), 25% higher odds of successful reperfusion (OR 1.25, 95% CI 1.08-1.44, I 2 = 42%), and 31% decrease in odds for mortality (OR 0.69, 95% CI 0.60-0.80, I 2 = 47%) compared with MT. sICH prevalence was similar between groups (OR 1.10, 95% CI 0.95-1.28, I 2 = 0%). Six of the studies were randomized controlled trials (RCTs) with intention-to-treat analysis done in patients presenting directly to MT-capable centers. When analysis was restricted to these 6 RCTs (n = 2,333), no differences were observed in functional independence (OR 1.08, 95% CI 0.91-1.27, I 2 = 0%), sICH (OR 1.37, 95% CI 0.95-1.97, I 2 = 0%), or mortality (OR 0.93, 95% CI 0.74-1.16, I 2 = 0%) between groups. However, successful reperfusion favored the BT group (OR 1.35, 95% CI 1.06-1.73, I 2 = 0%). DISCUSSION: The odds for functional independence, successful reperfusion, and mortality for the entire dataset favored the use of BT over MT (medium heterogeneity and low quality of evidence). When analysis was restricted to RCTs, both treatments had similar functional and safety outcomes (no heterogeneity), but recanalization rates favored the BT group (no heterogeneity). Because these findings may differ in patients who present to non-MT-capable centers or with the use of other thrombolytic agents, further RCTs are needed.

Efficacy and Safety of Using Dual Versus Monotherapy Antiplatelet Agents in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

BACKGROUND: Dual antiplatelet treatment (DAPT) with aspirin plus clopidogrel for a limited time is recommended after minor noncardioembolic stroke. METHODS: We performed a meta-analysis of all major studies that compared the efficacy and safety of DAPT versus monotherapy for the secondary prevention of recurrent stroke or transient ischemic attack. The primary outcomes were stroke and the composite of stroke, transient ischemic attack, acute coronary syndrome, and death from any cause. The safety outcome was major hemorrhage. Relative risk (RR) and 95% CIs were calculated. Heterogeneity was assessed by I2 and Cochrane Q statistics. RESULTS: The analysis included 27 358 patients, the quality of evidence was moderate to low, and the heterogeneity for all the comparisons was low (I2≤25%). Compared with monotherapy, DAPT reduced the risk of recurrent stroke (RR, 0.71 [95% CI, 0.63-0.81]) and composite outcome (RR, 0.76 [95% CI, 0.69-0.83]) but increased the risk of major bleeding (RR, 2.17 [95% CI, 1.45-3.25]). In the subgroup analysis, ≤30 days of DAPT increased the risk of hemorrhage relative to monotherapy (RR, 1.94 [95% CI, 1.08-3.52]). In the sensitivity analysis, the risk for hemorrhage with ≤30 days of DAPT after excluding the combination of aspirin plus ticagrelor was comparable to monotherapy (RR, 1.42 [95% CI, 0.77-2.60]). However, the risk for stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remain decreased compared with monotherapy. CONCLUSIONS: DAPT decreases the risk of recurrent stroke and composite events compared with monotherapy. DAPT increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus ticagrelor.

Severe acute respiratory syndrome coronavirus 2 infection in asymptomatic pediatric dental patients.

BACKGROUND: Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are typically asymptomatic but contagious. The authors investigated the positivity rate of asymptomatic SARS-CoV-2 infection in pediatric dental patients. METHODS: The authors reviewed consecutive charts of children younger than 18 years scheduled for elective dental procedures from April 1, 2020, through August 1, 2020. All patients were screened for signs and symptoms of SARS-CoV-2 infection. Asymptomatic patients scheduled for dental procedures underwent polymerase chain reaction (PCR) testing for SARS-CoV-2. Sociodemographic characteristics were abstracted, and positivity rates were calculated. Variables for patients who were SARS-CoV-2 positive and SARS-CoV-2 negative were compared using Fisher exact and Mann-Whitney U tests. RESULTS: The sample size was 921. The median age was 6 years, and 50.9% were boys. The overall SARS-CoV-2 positivity rate was 2.3%. Age, insurance status, medical history, and dental diagnosis were comparable in patients who were SARS-CoV-2 positive and SARS-CoV-2 negative. Positivity rates were statistically higher for Hispanic or Latinx patients than other groups (P = .038). CONCLUSIONS: Although the yield of testing was low, the systematic evaluation of asymptomatic pediatric dental cases via PCR resulted in the identification of SARS-CoV-2 carriers who could have been infectious. In this study, Hispanics or Latinx had a higher positivity rate than other demographic groups. PRACTICAL IMPLICATIONS: PCR testing for SARS-CoV-2 of asymptomatic patients in pediatric dentistry adds value to the use of screening questionnaires for the identification of infected people who could be contagious.

Systemic Immune-Inflammation (SII) index predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage.

BACKGROUND AND AIMS: In experimental models, enhanced inflammation contributes to secondary brain injury in spontaneous intracerebral hemorrhage (ICH). Several inflammatory markers have investigated in humans with inconclusive results. Here, we report the relationship between Systemic Immune-Inflammation (SII) Index and outcome. METHODS: We reviewed the medical records of 239 supratentorial spontaneous ICH patients. Patients were dichotomized based on modified Rankin Scale (mRS) at discharge in good (mRS 0-3) and poor (mRS 4-6) outcome. Demographic, clinical, laboratory and imaging data at admission were compared for both groups. SII index was calculated as [(Platelet counts x Absolute Neutrophil Counts (ANC)/Absolute Lymphocyte Counts (ALC))/1000]. Logistic regression analyses were performed to determine the association between markers of inflammation (ANC, ALC, Platelets, SII index) and outcome adjusting for baseline differences. RESULTS: Sixty-two percent of patients had poor outcome (median [IQR] age= 60 [52-71] years). Patients with poor outcome had lower Glasgow coma scale, larger hematoma volumes, and higher incidence of diabetes and intraventricular extension (p<0.05 for each variable). In univariate analysis, ANC and SII index were independently associated with poor outcome (p<0.05). In multivariate analysis, only SII index remained significantly associated with poor outcome (OR=1.34, 95% CI=1.04-1.72, p=0.02). ROC analysis showed that adjusted SII index is a good discriminator for poor outcome (AUC=0.89, 95% CI=0.84-0.93; P <0.0001), with the best cut-off value being 0.73 (Sensitivity 95%, Specificity 71%). CONCLUSIONS: In patients with supratentorial spontaneous ICH early SII index is an independent predictor of poor outcome at time of hospital discharge.

Neurology of Nutritional Deficiencies.

PURPOSE OF REVIEW: The goal of this chapter is to educate clinicians on the neurologic manifestations of certain nutritional deficiencies in order to promptly identify and appropriately treat these patients. RECENT FINDINGS: Many vitamin and nutritional deficiencies have been described dating back to the early days of neurology and medicine. Some are very rare and thus, there are no randomized controlled studies to assess supplementation or dosage; however, there are reviews of case reports that can assist clinicians in choosing treatments. While endemic vitamin and nutritional deficiencies may be rarely encountered in many countries, vulnerable populations continue to be at risk for developing neurologic complications. These populations include those with diseases causing malabsorption, the elderly, chronic alcohol users, as well as pregnant mothers with hyperemesis gravidarum to name a few. It is important to recognize syndromes associated with these nutritional deficiencies, as prompt identification and treatment may prevent permanent neurologic damage.

Intraventricular Hemorrhage Severity as a Predictor of Outcome in Intracerebral Hemorrhage.

Background/Objective: Intraventricular hemorrhage (IVH) extension after spontaneous supratentorial intracerebral hemorrhage (sICH) is an independent predictor of worse outcome. However, there is a paucity of data looking at the degree of IVH severity and its impact on outcome. This study addresses the contribution of IVH severity to outcome at time of hospital discharge after sICH. Methods: Two hundred and ten patients were included in the study. Baseline demographic and radiologic characteristics were abstracted. First available CT scans were reviewed for hematoma volume and location, IVH extension and presence of hydrocephalus (HCP). IVH severity was calculated using Graeb scale. Multivariate logistic regression models were developed to investigate the association of IVH severity with poor outcomes at hospital discharge, defined as modified Rankin scale score (mRS) >3. Results: Fifty-three percent of patients had IVH extension while 18% had surgical procedures done. Poor outcome (mRS >3) was seen for 56% of patients. Median IVH extension severity on the Graeb scale was two. Presence of IVH was associated with poor outcome in univariate and multivariate analysis (p < 0.005). Compared to patients with no IVH, IVH severity influenced outcome only when Graeb scores were ≥5 (OR = 1.3, 95% CI 0.49-3.23, p = 0.63, and OR = 2.9, 95% CI, 1.1-7.6, p = 0.03 for Graeb <5 and ≥5, respectively. Conclusions: Higher IVH severity (defined as Graeb score ≥5) is associated with worse outcome at time of hospital discharge, while lower IVH severity (Graeb scores 1-4) has similar outcomes to patients without IVH. IVH severity should be used in favor of IVH presence for prognostication purposes.

Implications of Janus Kinase 2 Mutation in Embolic Stroke of Unknown Source.

The role of genetic mutations in cerebral ischemia is not completely understood. Among these genetic variations, Philadelphia-negative gain-of-function mutation in the janus kinase 2 (JAK2) protein leads to overexpression of the genes involved in cell growth and proliferation, and has been linked to development of hematological malignancies, specifically, myeloproliferative neoplasms (MPNs; essential thrombocythemia [ET], polycythemia vera [PV], and primary myelofibrosis). Overt ET and PV are known to induce a prothrombotic state that leads to development of vascular complications, including cerebral arterial or venous thrombosis. Thromboembolism can precede overt presentation of an MPN by 2-3 years. As such, for the selected cases of embolic stroke or cerebrovascular sinus thrombosis with otherwise undetermined source and persistent thrombocytosis or polycythemia, in the absence of a confirmed MPN diagnosis, screening for JAK2 mutation may be reasonable, as early diagnosis and appropriate treatment can influence outcome by preventing recurrent thrombotic events. In this article, we review the literature on the genetics, pathogenesis, clinical manifestations, and treatment of JAK2-associated thrombosis, and present 2 cases of JAK2-associated cerebral arterial infarction and cerebral and systemic venous thromboembolism with otherwise negative etiology workup for stroke.

MR imaging findings in mild traumatic brain injury with persistent neurological impairment.

Traumatic brain injury (TBI) is a widespread cause of neurologic disability, with >70% of cases being mild in severity. Magnetic resonance imaging provides objective biomarkers in the diagnosis of brain injury by detecting brain lesions resulting from trauma. This paper reports on the detection rates of presumed trauma-related pathology using fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted imaging (SWI) in TBI patients with chronic, persistent symptoms. METHODS: 180 subjects with persistent neurobehavioral symptoms following head trauma referred by personal injury attorneys and 94 asymptomatic, age-matched volunteers were included in the study. 83% of TBI subjects were classified as mild. RESULTS: TBI subjects had a significantly greater number of lesions detected by FLAIR than controls (42% vs. 22%) and more lesions detected by SWI than controls (28% vs. 3%). To reduce the confounding effects of aging, we examined mild TBI subjects <45years of age, which reduced the rate of lesions detected by FLAIR (26% vs. 2%) and SWI (15% vs. 0%). This younger group, which contained few age-related lesions, also demonstrated that subcortical lesions on FLAIR are more specific for TBI than deeper lesions. CONCLUSIONS: While the presence of litigation in mild TBI cases with incomplete recovery has been associated with greater expression of symptomatology and, by extension, poorer outcomes, this study shows that mild TBI patients in litigation with chronic, persistent symptoms may have associated brain injury underlying their symptoms detectable by MRI biomarkers.

Magnetic resonance imaging signatures of vascular pathology in multiple sclerosis.

Venous vascular contributing factors to multiple sclerosis (MS) have been known for some time. Only recently has the scope of their potential role become more apparent with the theory of chronic cerebrospinal venous insufficiency (CCSVI). As research expands to further explore the role of vascular pathology in the MS population, it is expedient to review the evidence from an imaging perspective. In this paper, we review the current state-of-the-art methods using magnetic resonance imaging (MRI) as applied to imaging MS patients and CCSVI. This includes evaluating imaging signatures of vascular structure and flow as well as brain iron content. Upon review of the literature, we find that extracranial venous anomalies including stenosis, venous malformations, and collateralization of flow in the major veins of the neck have been observed to be prevalent in the MS population. Abnormal flow has been reported in MS patients both in major vessels using phase-contrast flow quantification and in the brain using perfusion-weighted imaging. We discuss the role of quantitative flow imaging and its potential in assessing possible biomarkers for abnormal flow. Finally, it has been suggested that the presence of high iron content may indirectly indicate progression of existing vascular pathology. To that end, we review the use of susceptibility-weighted imaging in monitoring iron in the thalamus, basal ganglia, and MS lesions.

Characteristics of flow through the internal jugular veins at cervical C2/C3 and C5/C6 levels for multiple sclerosis patients using MR phase contrast imaging.

OBJECTIVES: To study blood flow characteristics through the internal jugular veins (IJVs) at the cervical levels C2/C3 and C5/C6 in the neck of multiple sclerosis (MS) patients. METHODS: Magnetic resonance imaging at 3T was performed on 323 MS patients. Phase contrast imaging was used to quantify blood flow at both the C2/C3 and C5/C6 levels. Total IJV flow (tIJF) was normalized by total arterial flow (tAF). Contrast-enhanced time-resolved 3D MR arteriovenography and 2D time-of-flight MR venography were performed to assess IJV anatomy. Based on this assessment, the MS population was divided into non-stenotic (NST) and stenotic (ST) subjects. RESULTS: Of all the patients, 100 (31%) belonged to the NST group and 223 (69%) belonged to the ST group. At the C2/C3 and C5/C6 levels, the normalized tIJF of the ST group was 56±26% and 51±23%, respectively. This was significantly lower than that of the NST group, 85±13% and 73±12% (P<0·001). Zero percent and 5% of the NST group had a normalized tIJF of less than 50% at the C2/C3 and C5/C6 levels, compared to 37% and 47% for the ST group. The tAF was smaller for the secondary and primary progressive MS patients than the relapsing remitting MS patients (P = 0·02 and 0·01, respectively), while the tIJF was similar among all MS types. CONCLUSION: Total blood flow through the IJVs at both the C2/C3 and C5/C6 levels was reduced in the ST group compared to the NST group.

Quantitative flow measurements in the internal jugular veins of multiple sclerosis patients using magnetic resonance imaging.

PURPOSE: To study the blood flow through the internal jugular veins (IJVs) of the MS population. MATERIALS AND METHODS: Two hundred MS patients and 14 normal volunteers were evaluated with magnetic resonance imaging (MRI) at 3T. Contrast-enhanced time-resolved 3D MR angiography and 2D time-of-flight imaging were performed to assess abnormalities in the extracranial vascular anatomy. Based on this assessment, the MS population was divided into subgroups of non-stenotic (NST), cervical 1 stenotic only (C1ST) and cervical 6 stenotic (C6ST) subjects. In this study, 2D phase contrast MR imaging was used to quantify blood flow through major veins and arteries in the neck and flow differences among the groups were analyzed. RESULTS: Of the 200 MS patients, 87 (43.5%) belonged to the NST group, 50 (25%) belonged to the C1ST group and 63 (31.5%) belonged to the C6ST group. The total IJV flow normalized to the total arterial flow of the NST group was 75.12 ± 12.22 %. This was significantly higher than that of the C1ST group, 63.93 ± 16.08 % (p < 0.0001), which in turn was significantly higher than that of the C6ST group, 52.13 ± 20.71 % (p = 0.001). Seventy-nine percent of the stenotic groups had a normalized subdominant IJV flow of less than 20%, a combined IJV flow of less than 5o% and/or a sub-dominant IJV flow vs. dominant IJV flow ratio of less than 1/3. Only 2% of the NST group had a combined IJV flow of less than 50%, compared to 35% of the stenotic groups. CONCLUSION: Blood flow through the IJVs was reduced in the MS population with stenoses compared to those without.