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Administering Thrombolysis for Acute Ischemic Stroke in Patients Taking Direct Oral AnticoagulantsTo Treat or How to Treat
David J. Seiffge; Duncan Wilson, PhD; Teddy Yuan-Hao Wu, MD, PhD
doi : 10.1001/jamaneurol.2021.0287
JAMA Neurol. 2021;78(5):515-516
Direct oral anticoagulants (DOAC), the factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the direct thrombin inhibitor dabigatran, are emerging as anticoagulant treatment of choice for stroke prevention in patients with nonvalvular atrial fibrillation. Acute ischemic stroke occurs in 1% to 2% of DOAC-treated patients per year, and many would present within the standard therapeutic time window for intravenous thrombolysis and endovascular thrombectomy. This poses a significant clinical conundrum; it is likely that most patients with ischemic stroke taking DOACs are compliant with therapy, rendering the very medications used to prevent stroke the reason for withholding therapy. Current American Heart Association/American Stroke Association guidelines give a class III recommendation that thrombolysis might be harmful within 48 hours after last intake and should not be administered. Epidemiologic data published in 20211 suggest this may affect up to 18% of patients with atrial fibrillation who present with stroke1 who would be otherwise eligible for thrombolysis.
Complexities of Reperfusion Therapy in Patients With Ischemic Stroke Pretreated With Direct Oral AnticoagulantsTo Treat or Not, and How?
Alexandra L. Czap, MD; James C. Grotta, MD
doi : 10.1001/jamaneurol.2021.0290
JAMA Neurol. 2021;78(5):517-518
A rapidly increasing proportion of patients with acute ischemic stroke who are otherwise eligible for thrombolysis are excluded from this treatment because of possible or known concomitant direct oral anticoagulant (DOAC) treatment. Because the patient has had an ischemic stroke, the patient may not be effectively anticoagulated. The choice to either reverse the DOAC, followed by treatment with tissue plasminogen activator (tPA), or follow current American Heart Association/American Stroke Association guidelines1 and not treat the patient at all, if DOAC use is suspected within the past 48 hours, is not a decision for the faint of heart or the inexperienced. In the absence of a universally available rapid test to measure DOAC activity and the lack of standardized assay thresholds, the clinician who decides to treat must speculate on the coagulation status of the patient or consider blindly administering a costly and potentially risky reversal agent to treat the patient with a thrombolytic agent. Both reversing anticoagulation that has been prescribed for a prothrombotic or emboligenic condition and administering a thrombolytic to a patient receiving a DOAC are risky choices in which convincing data one way or the other are lacking and not likely to emerge from randomized clinical trials. Yet not reversing and treating may deprive the patient of the opportunity to escape long-term disability. There are many nuances to consider that would affect this decision. This Viewpoint will highlight several areas of uncertainty that a clinician must consider with thrombolysis treatment in patients exposed to DOACs.
No Time for This
Samuel Harrison Marcum, BS
doi : 10.1001/jamaneurol.2021.0481
JAMA Neurol. 2021;78(5):519-520
My stutter makes it hard for me to speak as quickly or as efficiently as people expect. To get through our morning rounds, we have to see 19 patients in 90 minutes. That is 1 patient every 4.7 minutes. He, the attending physician I am working with, has “no time for this,” and I have no time to unlock words. I know the problem list. In fact, I have rehearsed the problem list. Familiarity can loosen the lock on words and make them more acceptable. I could tell you all about the sepsis complicated by subsequent acute kidney injury and electrolyte imbalance. I could tell you about the imminent concern for seizures and cardiac arrest. But in this case, familiarity does not matter. I just cannot get it out. I keep quiet, and morning rounds march on.
JAMA Neurology—The Year in Review, 2020
S. Andrew Josephson, MD
doi : 10.1001/jamaneurol.2021.0123
JAMA Neurol. 2021;78(5):521-522
The last 12 months have been unprecedented here at JAMA Neurology. In the setting of the coronavirus disease 2019 (COVID-19) pandemic, the journal had to rapidly evolve to handle a record number of manuscripts and respond to the needs of our readers to be informed of the most timely and important neurological information about the virus. We received more than 400 submissions related to COVID-19, and we were able to publish very quickly those select contributions that we felt truly were important for neurologists on the frontlines, including the initial experience of neurological complications from Wuhan province, China, and important observations on the pathobiology of nervous system involvement.
Holding Out Hope After Traumatic Brain Injury
Jennifer A. Kim, MD, PhD; Kevin N. Sheth, MD
doi : 10.1001/jamaneurol.2020.5328
JAMA Neurol. 2021;78(5):522-524
Uncertainty of prognostication increases with more severe brain injury. Withdrawal of life-sustaining therapy (WLST) is often the proximate cause of death. Evidence suggests that level of consciousness may play a role in driving early WLST decisions.1 Studies have shown that many patients with traumatic brain injury (TBI) and other acute brain injuries regain consciousness within the first 72 hours, with most showing improvements in consciousness by 7 days after injury.2 However, the turning point at which a person who remains in a state of disordered consciousness will remain in this persistent state is still unclear. If no progress is seen in a patient’s arousal or awareness at 10 days or 2 weeks or 1 month, at what point do we consider pivoting our discussions about the likelihood of recovering consciousness?
A Link Between Cardiovascular Risk Management and Alzheimer Disease Is Still Elusive
Susan M. Landau, PhD; Theresa M. Harrison, PhD
doi : 10.1001/jamaneurol.2021.0083
JAMA Neurol. 2021;78(5):524-526
Alzheimer disease (AD) is the sixth leading cause of death in the US, but existing treatments provide only a modest improvement in symptoms. To our knowledge, no approved treatment exists that improves the course of disease or underlying pathology. Research on disease-modifying AD treatments has proven to be extremely challenging, with a number of major recent clinical trials of drug therapies resulting in negative or ambivalent findings.1,2 While many alternative ideas for developing a treatment for AD are being pursued, 2 key strategies have emerged: initiating interventions earlier in the course of disease in individuals who are at risk but unimpaired and identifying targets beyond abnormal amyloid and tau proteins, the pathology that defines AD.
Reperfusion Treatment and Stroke Outcomes in Hospitals With Telestroke Capacity
Andrew D. Wilcock, PhD; Lee H. Schwamm, MD; Jose R. Zubizarreta, PhD; et al.
doi : 10.1001/jamaneurol.2021.0023
JAMA Neurol. 2021;78(5):527-535
Importance Telestroke is increasingly used in hospital emergency departments, but there has been limited research on its impact on treatment and outcomes.
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome
Kerri L. LaRovere, MD; Becky J. Riggs, MD; Tina Y. Poussaint, MD; et al.
doi : 10.1001/jamaneurol.2021.0504
JAMA Neurol. 2021;78(5):536-547
Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear.
Recovery of Consciousness and Functional Outcome in Moderate and Severe Traumatic Brain Injury
Robert G. Kowalski, MBBCh, MS; Flora M. Hammond, MD; Alan H. Weintraub, MD; et al.
doi : 10.1001/jamaneurol.2021.0084
JAMA Neurol. 2021;78(5):548-557
Importance To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS).
Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM StudyA Randomized Clinical Trial
Ludwig Kappos, MD; Robert J. Fox, MD; Michel Burcklen, PhD; et al.
doi : 10.1001/jamaneurol.2021.0405
JAMA Neurol. 2021;78(5):558-567
Importance To our knowledge, the Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM) trial is the first phase 3 study comparing 2 oral disease-modifying therapies for relapsing multiple sclerosis (RMS).
Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer DiseaseSecondary Analysis of the SPRINT MIND Randomized Trial
Ilya M. Nasrallah, MD, PhD; Sarah A. Gaussoin, MS; Raymond Pomponio, BS; et al.
doi : 10.1001/jamaneurol.2021.0178
JAMA Neurol. 2021;78(5):568-577
Importance Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control.
Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children
Yi Li, MD; Wesley K. Thompson, PhD; Chase Reuter, MS; et al.
doi : 10.1001/jamaneurol.2021.0306
JAMA Neurol. 2021;78(5):578-587
Importance Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings.
Association Between Treatment Progression, Disease Refractoriness, and Burden of Illness Among Hospitalized Patients With Status Epilepticus
Elan L. Guterman, MD; John P. Betjemann, MD; Alex Aimetti, PhD; et al.
doi : 10.1001/jamaneurol.2021.0520
JAMA Neurol. 2021;78(5):588-595
Importance Status epilepticus (SE) is associated with poor clinical outcomes and high cost. Increased levels of refractory SE require treatment with additional medications and carry increased morbidity and mortality, but the associations between SE refractoriness, clinical outcomes, and cost remain poorly characterized.
Association of Pharmacological Interventions With Symptom Burden Reduction in Patients With Mild Traumatic Brain InjuryA Systematic Review
Charles Feinberg, BA; Catherine Carr, MLIS; Roger Zemek, MD; et al.
doi : 10.1001/jamaneurol.2020.5079
JAMA Neurol. 2021;78(5):596-608
Importance Mild traumatic brain injury (TBI) is experienced by 55.9 million people globally each year. The symptoms of mild TBI are diverse and sometimes long-lasting, requiring frequent use of pharmacological interventions to mitigate them. A thorough understanding of the data supporting pharmacological interventions is important for decision-making among clinicians treating this common injury.
Absent Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging Activation of the Orbitofrontal Cortex in a Patient With Persistent Cacosmia and Cacogeusia After COVID-19 Infection
Ismail Ibrahim Ismail, MSc; Khaled A. Gad, MD
doi : 10.1001/jamaneurol.2021.0009
JAMA Neurol. 2021;78(5):609-610
25-year-old woman with no relevant medical history developed fever, generalized body pain, dry cough, anosmia, and ageusia in April 2020. She was diagnosed with coronavirus disease 2019 (COVID-19) by positive findings on polymerase chain reaction assay and positive findings on computed tomography of the chest. Her clinical course was uncomplicated, and she was treated conservatively. Anosmia and ageusia started to improve during the following month. However, during the recovery phase, she started to experience offensive odor (cacosmia) and taste (cacogeusia) with stimulation of these sensations. Ear, nose, and throat evaluation showed normal clinical and endoscopic nasal examination findings. Computed tomography findings of the paranasal sinuses were unremarkable. She was given oral and intranasal corticosteroids, in addition to multivitamins, zinc, and olfactory training. However, her symptoms persisted for 3 months, and she was referred to our neurology clinic for further evaluation. Findings of her neurological examination were normal.
The Trade-off Between the Bony Carotid Canal and Internal Carotid Artery
Lizhang Chen, MD; Hua Cao, MD; Muke Zhou, MD
doi : 10.1001/jamaneurol.2021.0344
JAMA Neurol. 2021;78(5):611-612
A 24-year-old woman presented with sudden-onset slurred speech and right-side weakness. Ten months previously, she had had an episode of transient consciousness loss. The patient denied smoking, had no history of miscarriage, was not taking oral contraceptives, and had a body mass index (calculated as weight in kilograms divided by height in meters squared) of 21.2. She denied any family history of stroke. On admission, her blood pressure was 103/65 mm Hg in the right arm and 76/40 mm Hg in the left arm. Her body temperature, heartbeat, and respiration rate were within normal limits. Simultaneous palpation of pulses in the 2 arms revealed that the left radial pulse was weak. A neurological examination revealed clinically significant right-side hemiparesis and dysarthria. Other findings of general physical and neurological examinations were normal. The patient’s blood work results were unremarkable, aside from an elevated erythrocyte sedimentation rate (90.0 mm/h) and C-reactive protein level (4.06 mg/dL [to convert to milligrams per liter, multiply by 10.0]). Hypercoagulable laboratory studies, chest radiography, transthoracic echocardiography, electrocardiography, and 24-hour Holter monitoring yielded normal findings. Head computed tomography (CT) images showed an acute infarct in the left basal ganglia. Head-and-neck CT angiography with digital subtraction angiography revealed left carotid artery occlusion and subclavian artery stenosis (Figure 1). These findings were believed to be consistent with Takayasu arteritis. The patient was given prednisolone (initial dosage, 60 mg/d, tapered very slowly). Regular clinical follow-up, including physical examinations, radiographic evaluations, and other medical tests, was performed every 6 to 12 months.
Headache, Cognitive Decline, and a Curious Rim-Enhancing Lesion
Charles B. Beaman, MD, PhD; Antonio Spagnolo-Allende, MD, MPH; Chun-Chieh Lin, MD, PhD
doi : 10.1001/jamaneurol.2021.0161
JAMA Neurol. 2021;78(5):613-614
A 75-year-old man presented with several weeks of intermittent headache that had progressed to severe, persistent headache with right eye pain. He had hypertension, hyperlipidemia, diabetes, and atrial fibrillation. He denied tobacco, alcohol, or drug use. A neurological examination was notable for disorientation to the month, deficits in short-term memory, and an upward drift of the left arm. Cranial nerve, sensory, coordination, and deep tendon reflex examinations were normal. He walked with a slightly wide but steady gait. His serum red and white blood cell counts, coagulation profile, and electrolyte levels were within normal limits. Blood cultures had negative results. A 24-hour electroencephalogram showed right hemispheric slowing and multiple right centroparietal seizures of 1 minute each, without noticeable clinical correlates. A magnetic resonance image (MRI) of the brain was remarkable for a large T2-hyperintense lesion in the right temporoparietal region, with an increased diffusion-weighted imaging (DWI) signal (low apparent diffusion coefficient), a low signal on susceptibility-weighted imaging, increased T1 signal intensity in and around the lesion, and a contrast-enhancing rim with leptomeningeal enhancement (Figure 1). A smaller satellite lesion with a similar MRI profile was noted inferiorly in the right anterior temporal lobe. A computed tomography scan of the chest, abdomen, and pelvis did not show any metastatic disease. A cerebrospinal fluid (CSF) profile showed a normal red blood cell count and protein and glucose levels and a mildly elevated white blood cell count of 11 cells/?L (to convert to cells?×?109/L, multiply by 0.001). The fluid was absent oligoclonal bands and had negative bacterial and fungal culture results, a meningitis-encephalitis polymerase chain reaction panel, and a paraneoplastic panel. Cytology and flow cytometry had negative results. The patient then underwent surgical biopsy of the temporoparietal lesion.
Local Cerebral Recombinant Tissue Plasminogen Activator Concentrations During Acute Stroke
Fabian Essig, MD; Alexander M. Kollikowski, MD; Wolfgang Müllges, MD; et al.
doi : 10.1001/jamaneurol.2021.0065
JAMA Neurol. 2021;78(5):615-617
Residual Fatigue and Cognitive Deficits in Patients After Leucine-Rich Glioma-Inactivated 1 Antibody Encephalitis
Sophie N. M. Binks, MD; Michele Veldsman, PhD; Ava Easton, PhD; et al.
doi : 10.1001/jamaneurol.2021.0477
JAMA Neurol. 2021;78(5):617-619
Insights on Intensive vs Nonintensive Prerandomization Systolic Blood Pressure Reduction
Chakrapani Mahabala, MD; Prabodh Varma, MBBS; Ashok Shenoy, MD
doi : 10.1001/jamaneurol.2021.0258
JAMA Neurol. 2021;78(5):619-620
To the Editor We have read the article titled “Outcomes of Intensive Systolic Blood Pressure Reduction in Patients With Intracerebral Hemorrhage and Excessively High Initial Systolic Blood Pressure: Post Hoc Analysis of a Randomized Clinical Trial” by Qureshi et al,1 published online in JAMA Neurology on September 8, 2020. We would like to congratulate the authors for this successful analysis and make some comments and contributions.
Insights on Intensive Vs Nonintensive Prerandomization Systolic Blood Pressure Reduction—Reply
Adnan I. Qureshi, MD; Wei Huang, MA; Iryna Lobanova, MD, PhD
doi : 10.1001/jamaneurol.2021.0261
JAMA Neurol. 2021;78(5):620
In Reply We thank Mahabala et al for their letter. We performed the analysis using postrandomization treatment groups based on systolic blood pressure (SBP) target values (intensive-arm goal, 110-139 mm Hg; standard-arm goal, 140-179 mm Hg).1 The first SBP level recorded in the emergency department was termed the initial SBP. The protocol permitted initiation of antihypertensive treatment (often by intravenous nicardipine infusion) before randomization to lower the SBP level to less than 180 mm Hg,2 which was consistent with the contemporary American Stroke Association Stroke Council guidelines,3 but the SBP level was to be maintained at 140 mm Hg or more before randomization. The initiation of antihypertensive treatment before randomization resulted in prerandomization SBP level reduction in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. The issue regarding prerandomization or ultra-early intensive reduction of SBP being more beneficial than intensive SBP reduction at later points has been raised previously.4 Mahabala et al have provided a valuable analysis of the data supporting the hypothesis in their letter. Li et al4 also reported that among 354 patients in whom intravenous nicardipine treatment was initiated within 2 hours, the frequency of hematoma expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group. Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma expansion, a higher rate of functional independence, and good outcome at 90 days. One issue to be cautious about in prerandomization SBP reduction is that the SBP reduction groups are created based on post hoc conceptualization. Therefore, the limitations of post hoc analysis apply and should be taken into account during interpretation.
Error in Author Name
doi : 10.1001/jamaneurol.2021.0456
JAMA Neurol. 2021;78(5):620
In the Original Investigation titled “Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis,” published in the January 2021 issue of JAMA Neurology,1 the 23rd author’s first name was misspelled. Dr Wang’s name should be spelled “Li-San Wang.” This article was corrected online.
JAMA Neurology Peer Reviewers in 2020
doi : 10.1001/jamaneurol.2021.0212
JAMA Neurol. 2021;78(5):e210212
JAMA Neurology
doi : 10.1001/jamaneurol.2020.3661
JAMA Neurol. 2021;78(5):514
Mission Statement: The mission of JAMA Neurology is to publish scientific information primarily important for those physicians caring for people with neurologic disorders but also for those interested in the structure and function of the normal and diseased nervous system. These specific aims are (1) to make timely publication of original research of the nervous system, (2) to record observations of single patients or groups of patients that will provide new information and insights, (3) to report more basic research that is pertinent to the understanding of disease, (4) to introduce topics of practice, ethics, teaching, and history that are useful, and (5) to provide a forum for discussion on topics that may be controversial in this field. This information will be published only after extensive peer review so that originality, clarity, and precision are ensured.
