sabato 26 agosto 2017
Association of JNC-8 and SPRINT Systolic Blood Pressure Levels With Cognitive Function and Related Racial Disparity
Importance The Eighth Joint National Committee (JNC-8) recommended treating systolic blood pressure (SBP) to a target below 150 mm Hg in older adults, whereas data from the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that a SBP level of lower than 120 mm Hg decreases cardiovascular event rates. Target SBP guidelines have not addressed the potential that black patients may have greater morbidity and mortality from hypertension, especially with regard to cognitive outcomes. The association of these discordant SBP targets with cognition and differences by race have not been systematically evaluated in the same population.
Objectives To assess the long-term outcomes of the various recommended SBP levels and to determine if racial differences exist based on long-term cognitive trajectories.
Design, Setting, and Participants A total of 1657 cognitively intact older adults receiving treatment for hypertension were studied from 1997 to 2007 in the Health Aging and Body Composition study. Data analysis was conducted from October 1, 2016, to January 1, 2017.
Main Outcomes and Measures Cognition was assessed using the Modified Mini-Mental State Examination (3MSE) 4 times and the Digit Symbol Substitution Test (DSST) 5 times. At each visit, participants were classified as having an SBP level of 120 mm Hg or lower, 121 to 139 mm Hg, 140 to 149 mm Hg, or 150 mm Hg or higher based on the mean SBP level of 2 seated readings. Mixed models assessed the association of SBP levels with 10-year cognitive trajectories. The impact of race was tested using a race interaction term.
Results During the 10-year study period, among the 1657 individuals (908 women and 784 black patients; mean [SE] age, 73.7 [0.1] years), there was a differential decrease in 3MSE and DSST scores by the SBP levels, with the greatest decrease in the group with SBP levels of 150 mm Hg or higher (adjusted decrease was 3.7 for 3MSE and 6.2 for DSST) and the lowest decrease in the group with SBP levels of 120 mm Hg or lower (adjusted decrease was 3.0 for 3MSE and 5.0 for DSST) (P < .001 for both). Compared with white patients, black patients had a greater difference between the higher and lower SBP levels in the decrease in cognition; adjusted differences between the group with SBP levels of 150 mm Hg or higher and the group with SBP levels of 120 mm Hg or lower were –0.05 in white patients and –0.08 in black patients for 3MSE (P = .03) and –0.07 in white patients and –0.13 in black patients for DSST (P = .05).
Conclusions and Relevance For patients 70 years of age or older receiving treatment for hypertension, a SPRINT SBP level of 120 mm Hg or lower was not associated with worsening cognitive outcome and may be superior to the JNC-8 target for cognition. Lower SBP treatment levels may result in improved cognition in black patients.
JAMA Neurology 2017
Association of Childhood Body Mass Index and Change in Body Mass Index With First Adult Ischemic Stroke
Importance The incidence of ischemic stroke among young adults is rising and is potentially due to an increase in stroke risk factors occurring at younger ages, such as obesity.
Objectives To investigate whether childhood body mass index (BMI) and change in BMI are associated with adult ischemic stroke and to assess whether the associations are age dependent or influenced by birth weight.
Design, Setting, and Participants This investigation was a population-based cohort study of schoolchildren born from 1930 to 1987, with follow-up through national health registers from 1977 to 2012 in Denmark. Participants were 307 677 individuals (8899 ischemic stroke cases) with measured weight and height at ages 7 to 13 years. The dates of the analysis were September 1, 2015, to May 27, 2016.
Main Outcomes and Measures Childhood BMI, change in BMI, and birth weight. Ischemic stroke events were divided into early (≤55 years) or late (>55 years) age at diagnosis.
Results The study cohort comprised 307 677 participants (approximately 49% female and 51% male). During the study period, 3529 women and 5370 men experienced an ischemic stroke. At all ages from 7 to 13 years, an above-average BMI z score was positively associated with early ischemic stroke. At age 13 years, a BMI z score of 1 was associated with hazard ratios (HRs) of 1.26 (95% CI, 1.11-1.43) in women and 1.21 (95% CI, 1.10-1.33) in men. No significant associations were found for below-average BMI z scores. Among children with above-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.10; 95% CI, 1.01-1.20) and in men (HR, 1.08; 95% CI, 1.00-1.16). Similarly, among children with below-average BMI z scores at age 7 years, a score increase of 0.5 from ages 7 to 13 years was positively associated with early ischemic stroke in women (HR, 1.14; 95% CI, 1.06-1.23) and in men (HR, 1.10; 95% CI, 1.04-1.18). Adjusting for birth weight minimally affected the associations.
Conclusions and Relevance Independent of birth weight, above-average childhood BMI and increases in BMI during childhood are positively associated with early adult ischemic stroke. To avoid the occurrence of early ischemic stroke associated with childhood overweight and obesity, these results suggest that all children should be helped to attain and maintain healthy weights.
JAMA Neurology 2017
domenica 20 agosto 2017
Cerebral venous thrombosis (CVT) is an important cause of stroke in young adults. Data from large international registries published in the past two decades have greatly improved our knowledge about the epidemiology, clinical manifestations and prognosis of CVT. The presentation of symptoms is highly variable in this disease, and can range from a patient seen at the clinic with a 1-month history of headache, to a comatose patient admitted to the emergency room. Consequently, the diagnosis of CVT is often delayed or overlooked. A variety of therapies for CVT are available, and each should be used in the appropriate setting, preferably guided by data from randomized trials and well-designed cohort studies. Although deaths from CVT have decreased in the past few decades, mortality remains ~5–10%. In this Review, we provide a comprehensive and contemporary overview of CVT in adults, with emphasis on advancements made in the past decade on the epidemiology and treatment of this multifaceted condition.
Nature Reviews Neurology 2017
Importance Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients.
Objectives To investigate the clinical spectrum associated with KCNB1 variants and the genotype-phenotype correlations.
Design, Setting, and Participants This study summarized the clinical and genetic information of patients with a presumed pathogenic variant in KCNB1.Patients were identified in research projects or during clinical testing. Information on patients from previously published articles was collected and authors contacted if feasible. All patients were seen at a clinic at one of the participating institutes because of presumed genetic disorder. They were tested in a clinical setting or included in a research project.
Main Outcomes and Measures The genetic variant and its inheritance and information on the patient's symptoms and characteristics in a predefined format. All variants were identified with massive parallel sequencing and confirmed with Sanger sequencing in the patient. Absence of the variant in the parents could be confirmed with Sanger sequencing in all families except one.
Results Of 26 patients (10 female, 15 male, 1 unknown; mean age at inclusion, 9.8 years; age range, 2-32 years) with developmental delay, 20 (77%) carried a missense variant in the ion channel domain of KCNB1, with a concentration of variants in region S5 to S6. Three variants that led to premature stops were located in the C-terminal and 3 in the ion channel domain. Twenty-one of 25 patients (84%) had seizures, with 9 patients (36%) starting with epileptic spasms between 3 and 18 months of age. All patients had developmental delay, with 17 (65%) experiencing severe developmental delay; 14 (82%) with severe delay had behavioral problems. The developmental delay was milder in 4 of 6 patients with stop variants and in a patient with a variant in the S2 transmembrane element rather than the S4 to S6 region.
Conclusions and Relevance De novo KCNB1 missense variants in the ion channel domain and loss-of-function variants in this domain and the C-terminal likely cause neurodevelopmental disorders with or without seizures. Patients with presumed pathogenic variants in KCNB1 have a variable phenotype. However, the type and position of the variants in the protein are (imperfectly) correlated with the severity of the disorder.
JAMA Neurology 2017
Importance There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.
Objective To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis.
Design, Setting, and Participants A prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.
Interventions Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase–polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected.
Main Outcomes and Measures The detection of neurologic complications secondary to ZIKV infection.
Results Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5).
Conclusions and Relevance In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.
JAMA Neurology 2017