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Perils of Race-Based Norms in Cognitive TestingThe Case of Former NFL Players
Katherine L. Possin, PhD; Elena Tsoy, PhD; Charles C. Windon, MD
doi : 10.1001/jamaneurol.2020.4763
JAMA Neurol. 2021;78(4):377-378
The landmark National Football League (NFL) Players’ Concussion Injury Litigation case, which brought to public attention the high prevalence of neurodegenerative disorders among former players, has now exposed a major weakness in the field of neuropsychology: the use of race-adjusted norms as a crude proxy for lifelong social experience. Under the settlement agreement, retired NFL players who undergo cognitive testing and meet criteria for neurodegenerative disorders may be eligible for substantial monetary awards. In a new class action lawsuit filed on August 25, 2020, Kevin Henry and Najeh Davenport, 2 retired players who were diagnosed as having dementia but later denied benefits, accused the NFL of systematically discriminating against Black players filing dementia-related settlement claims. The plaintiffs allege that the NFL has “repeatedly insisted that applicants’ scores must be race normed by using separate Black and White reference populations—a position that greatly reduces Black players’ chances of success.”1 In this Viewpoint, we explain the practice and perils of using race-adjusted norms and propose a new approach that could replace the current standard.
The Future Is P-Tau—Anticipating Direct-to-Consumer Alzheimer Disease Blood Tests
Emily A. Largent, JD, PhD, RN; Anna Wexler, PhD; Jason Karlawish, MD
doi : 10.1001/jamaneurol.2020.4835
JAMA Neurol. 2021;78(4):379-380
Recent studies suggest blood levels of phosphorylated tau (p-tau) isoforms can detect both the tau and amyloid pathologies that define Alzheimer disease (AD).1 More research is needed to replicate these results in large, diverse cohorts and quantify a p-tau blood test’s ability to prognosticate the onset of dementia. Nevertheless, we anticipate that the ability to receive diagnostic and prognostic information with the ease of a blood test will revolutionize AD research and care. We also anticipate that it will be the basis of a profitable direct-to-consumer (DTC) test, one that highlights considerable ethical and social challenges of DTC testing and AD.
No Visitors Allowed
Elizabeth Cuevas, MD
doi : 10.1001/jamaneurol.2021.0050
JAMA Neurol. 2021;78(4):381-382
To Screen or Not to Screen for Carotid StenosisIs That the Question?
Seemant Chaturvedi, MD
doi : 10.1001/jamaneurol.2020.5382
JAMA Neurol. 2021;78(4):383-384
Screening for asymptomatic internal carotid artery (ICA) stenosis has been a controversial topic for many years. In 1995, the Asymptomatic Carotid Atherosclerosis Study (ACAS) was published, showing a reduction in ipsilateral stroke among patients with stenosis of 60% to 99% who underwent carotid endarterectomy (CEA).1 This led to a sharp rise in the volume of CEA procedures and calls to screen middle-aged and elderly individuals with no symptoms of a recent transient ischemic attack or ischemic stroke.
Effect of Motor Skill Training in Functional Activities vs Strength and Flexibility Exercise on Function in People With Chronic Low Back PainA Randomized Clinical Trial
Linda R. van Dillen, PhD; Vanessa M. Lanier, DPT; Karen Steger-May, MA
doi : 10.1001/jamaneurol.2020.4821
JAMA Neurol. 2021;78(4):385-395
Importance Chronic low back pain (LBP) is the most prevalent chronic pain in adults, and there is no optimal nonpharmacologic management. Exercise is recommended, but no specific exercise-based treatment has been found to be most effective.
Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease
Alexis Moscoso, PhD; Michel J. Grothe, PhD; Nicholas J. Ashton, PhD
doi : 10.1001/jamaneurol.2020.4986
JAMA Neurol. 2021;78(4):396-406
Importance Plasma phosphorylated tau at threonine 181 (p-tau181) has been proposed as an easily accessible biomarker for the detection of Alzheimer disease (AD) pathology, but its ability to monitor disease progression in AD remains unclear.
Association of Glycolysis-Enhancing ?-1 Blockers With Risk of Developing Parkinson Disease
Jacob E. Simmering, PhD; Michael J. Welsh, MD; Lei Liu, PhD
doi : 10.1001/jamaneurol.2020.5157
JAMA Neurol. 2021;78(4):407-413
Importance Parkinson disease (PD) is a common neurodegenerative disease. A treatment that prevents or delays development of PD is a critical unmet need. Terazosin and closely related drugs were recently discovered to enhance glycolysis and reduce PD progression in animal models and human clinical databases.
Identifying the Distinct Cognitive Phenotypes in Multiple Sclerosis
Ermelinda De Meo, MD; Emilio Portaccio, MD; Antonio Giorgio, MD
doi : 10.1001/jamaneurol.2020.4920
JAMA Neurol. 2021;78(4):414-425
Importance Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.
Comparison of Corticosteroid Tapering Regimens in Myasthenia GravisA Randomized Clinical Trial
Tarek Sharshar, MD, PhD; Raphaël Porcher, PhD; Sophie Demeret, MD
doi : 10.1001/jamaneurol.2020.5407
JAMA Neurol. 2021;78(4):426-433
Importance The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated.
Thrombectomy for Primary Distal Posterior Cerebral Artery Occlusion StrokeThe TOPMOST Study
Lukas Meyer, MD; Christian Paul Stracke, MD; Noël Jungi, MD
doi : 10.1001/jamaneurol.2021.0001
JAMA Neurol. 2021;78(4):434-444
Importance Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse.
Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer DiseaseResults From 2 Phase III Clinical Trials
Ming Lu, MS, MPH, MD; Michael J. Pontecorvo, PhD; Michael D. Devous Sr, PhD
doi : 10.1001/jamaneurol.2020.5505
JAMA Neurol. 2021;78(4):445-453
Importance Flortaucipir positron emission tomography (PET) scans, rated with a novel, US Food and Drug Administration–approved, clinically applicable visual interpretation method, provide valuable information regarding near-term clinical progression of patients with Alzheimer disease (AD) or mild cognitive impairment (MCI).
Seizure Cycles in Focal Epilepsy
Marc G. Leguia, PhD; Ralph G. Andrzejak, PhD; Christian Rummel, PhD
doi : 10.1001/jamaneurol.2020.5370
JAMA Neurol. 2021;78(4):454-463
Importance Focal epilepsy is characterized by the cyclical recurrence of seizures, but, to our knowledge, the prevalence and patterns of seizure cycles are unknown.
Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets
Demis A. Kia, MBBS; David Zhang, MSc; Sebastian Guelfi, PhD
doi : 10.1001/jamaneurol.2020.5257
JAMA Neurol. 2021;78(4):464-472
Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD.
Agent Orange Exposure and Dementia Diagnosis in US Veterans of the Vietnam Era
Steven Martinez, BS; Kristine Yaffe, MD; Yixia Li, MPH
doi : 10.1001/jamaneurol.2020.5011
JAMA Neurol. 2021;78(4):473-477
Importance Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated with increased risk of a wide range of conditions, including neurologic disorders (eg, Parkinson disease), metabolic disorders (eg, type 2 diabetes), and systemic amyloidosis, the association between Agent Orange and dementia remains unclear.
Long-term Socioeconomic Outcomes Associated With Pediatric-Onset Multiple Sclerosis
Kyla A. McKay, PhD; Emilie Friberg, PhD; Neda Razaz, PhD
doi : 10.1001/jamaneurol.2020.5520
JAMA Neurol. 2021;78(4):478-482
Importance Pediatric-onset multiple sclerosis (PoMS) is associated with significant cognitive and physical disability. Whether this disability translates into differences in educational achievements and earnings is unknown.
Adolescent-Onset and Adult-Onset Vitamin-Responsive Neurogenetic DiseasesA Review
Daniele Mandia, MD; Natalia Shor, MD; Jean-François Benoist, PharmD, PhD
doi : 10.1001/jamaneurol.2020.4911
JAMA Neurol. 2021;78(4):483-490
Importance Vitamin-responsive inherited diseases are among the rare genetic disorders with a specific pharmacological treatment. Many of these conditions have a prominent neurological phenotype that is mainly reported in children. Being rare and often strikingly different in adult-onset forms, they are still poorly known in the medical fields specific to adults.
Cortical Vein Thrombosis, Tortuous Venous Vasculature, and Microhemorrhages in Neurosarcoidosis
Ryan Kammeyer, MD, MSE; Teri Schreiner, MD, MPH
doi : 10.1001/jamaneurol.2020.5440
JAMA Neurol. 2021;78(4):491-492
A previously healthy 13-year-old boy presented with an episode of left-sided facial droop and dysarthria lasting 90 minutes. His initial brain magnetic resonance imaging (MRI) demonstrated a nonenhancing fluid-attenuated inversion recovery hyperintensity in the corpus callosum and right cerebellar peduncle. Small tortuous veins were noted near the peduncular lesion, and punctate foci of susceptibility were noted in the area of the caudate, thalamus, and cerebellum. These were interpreted as a developmental venous anomaly and nonspecific prior injury, respectively. Serum anti–myelin oligodendrocyte glycoprotein and anti–aquaporin-4 antibodies tests were negative, and analysis of cerebrospinal fluid was normal except for a mild lymphocytic pleocytosis (7 leukocytes/mm3 with 1 red blood cell count/mm3) with a negative infectious evaluation. He was monitored closely every 3 months for clinical or radiographic progression. His MRI 8 months after presentation was notable for new and evolving T2 hyperintensities, with linear enhancement along the prior cerebellar lesion, and unchanged focal venous tortuosity and microhemorrhages. Despite several atypical features, this was interpreted as radiographic progression of presumed multiple sclerosis (MS), and he started rituximab infusions.
Bilateral Vagus Nerve Enhancement in a Patient With Leptomeningeal Lymphoplasmacytic Lymphoma Presenting with Intractable Hiccups
Rafid Mustafa, MD; Bryan J. Neth, MD, PhD; Derek Stitt, MD
doi : 10.1001/jamaneurol.2020.4830
JAMA Neurol. 2021;78(4):493-494
A 73-year-old man was admitted with intractable hiccups. His history was notable for lymphoplasmacytic lymphoma (LPL) diagnosed several years prior when he presented with fatigue and was found to have serum IgM ? monoclonal protein with an M spike and a hypercellular bone marrow biopsy with lymphoplasmacytic features. He was initially treated with a chemotherapeutic regimen of rituximab, cyclophosphamide, vincristine, and prednisone. In the setting of progressive disease, he ultimately underwent autologous peripheral blood stem cell transplant. Serial monitoring thereafter revealed normal complete blood cell counts.
Living to Dream
Donald L. Bliwise, PhD; Lynn Marie Trotti, MD, MSc
doi : 10.1001/jamaneurol.2021.0053
JAMA Neurol. 2021;78(4):495
To the Editor We read with great enthusiasm the fascinating report by Leary et al1 that lower rapid eye movement (REM) sleep amounts are associated with reduced survival, a finding sufficiently robust to withstand adjustments for sleep apnea, abnormal sleep duration, imminent death, and depression and independently replicated in another cohort. The accompanying Editorial2 posed the provocative question of whether this finding might have any practical use to a clinical neurologist. A separate question raised from these data is whether interindividual variability in REM percentage, compared with other sleep features, might provide another clue to REM’s biological importance. As evidenced by coefficients of variation (COV) (SD?/?mean?×?100) for REM percentage within these cohorts, 34.4% for the Outcomes of Sleep Disorders in Older Men (MrOS) Sleep Study and 36.9% for the Wisconsin Sleep Cohort (WSC), differences across individuals in this measure are quite small. By contrast, their magnitude is greatly exceeded by COVs of conditions with known morbidity that neurologists typically treat, such as sleep apnea, for which COVs for the apnea hypopnea index (with a mean calculated across quartiles) were 75.7% and 131.6% for the MrOS and WSC studies, respectively, and for periodic leg movements (often treated when accompanied by restless legs), for which COVs (with a mean calculated across quartiles) were 105.1% and 84.9% for the MrOS and WSC studies, respectively. Apart from disease, perhaps even more striking were the restricted REM COVs in comparison with other prominent sleep architecture features not constituting disease in their own right. For the percentage in N3 (78.4% and 76.6% for the MrOS and WSC studies, respectively), a stage fundamentally constituted by slow waves, the loss of which is often considered to reflect decreased synaptic density and memory consolidation deficits,3,4 COVs were twice as large. The current article1 is not the first report from the MrOS study suggesting that REM, rather than N3, may hold greater significance in this cohort,5 although the finding’s resilience in the WSC study (with similar REM COVs), greatly enhances the likelihood of generalizability.
Living to Dream—Reply
Eileen B. Leary, PhD, RPSGT; Katie L. Stone, PhD; Emmanuel Mignot, MD, PhD
doi : 10.1001/jamaneurol.2021.0056
JAMA Neurol. 2021;78(4):495-496
In Reply We thank Bliwise and Trotti for their interest in our findings showing that lower amounts of rapid eye movement (REM) sleep were associated with increased rates of mortality in 2 distinct population-based studies.1 Since this article1 was published, we have tested our findings in a third cohort, the Sleep Heart Health Study, and observed consistent outcomes (hazard ratio, 1.13 [95% CI, 1.07-1.18]). The Sleep Heart Health Study includes 5550 participants (47.6% men; 84.6% white) of a mean (SD) age of 63.0 (11.2) years at baseline who were monitored for a median of 11.9 years. A meta-analysis of all 3 cohorts yielded an overall hazard ratio of 1.13 (95% CI, 1.10-1.17; overall effect P?<?.001) for all-cause mortality in more than 10?000 participants, making it an extraordinarily robust finding across a broad age range and diverse racial/ethnic groups.2
Risk of Hemorrhagic Stroke in Patients With Coronavirus Disease 2019
Michael Silverman, MD; Megan Devlin, MD; Michal Krawczyk, MD
doi : 10.1001/jamaneurol.2021.0117
JAMA Neurol. 2021;78(4):496-497.
Risk of Hemorrhagic Stroke in Patients With Coronavirus Disease 2019—Reply
Alexander E. Merkler, MD, MS; Cenai Zhang, MS; Babak B. Navi, MD, MS
doi : 10.1001/jamaneurol.2021.0120
JAMA Neurol. 2021;78(4):497
Error in Author Name and Change to Open Access
doi : 10.1001/jamaneurol.2021.0103
JAMA Neurol. 2021;78(4):497
