Every year, we ask members of our editorial advisory board — all leaders in their respective fields — to reflect on the most important advances, policies, and professional issues that occurred during the past 12 months. Here, in the "Best Advances of 2016," our editorial team sheds light on developments that were both incremental and transformational this past year. Read on to learn more about those advances — and why they are important — in such areas as ethics and professionalism, stroke, epilepsy, dementia, multiple sclerosis, neurogenetics, and peripheral neuropathy, to name a few. This year, too, we feature advances from some of the major neurology meetings held in 2016, including highlights of top-scored abstracts selected by the Science Committees.
David J. Gill, MD, cognitive and behavioral neurologist, Unity Rehabilitation and Neurology, Rochester, NY.
The Pick: Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of dementia over three decades in the Framingham Heart Study. N Engl J Med 2016:374(6): 523-532.
The Findings: This study used data from the longitudinal Framingham Heart Study to look at age- and gender-adjusted dementia incidence over a 30-year period, from 1977 to 2008, and compared dementia incidence by four-year time periods. The results showed that the incidence of dementia decreased from the first to last time period. The decrease in incidence of dementia remained even after the prevalence of vascular risk factors was accounted for, suggesting an effect in addition to the improvement in control of cardiovascular risk factors over the past 30 years.
Why It's Important: This study is significant for several reasons. First, it reinforces the value of large-scale longitudinal epidemiological studies. Second, it provides data to suggest that the models predicting very large increases in the prevalence of dementia may not be accurate. While this is a single study, it is based on longitudinal data and the results should not be ignored. Further analysis of this data set and other studies may help to identify what factors other than control of cardiovascular risk factors may account for the decrease in incidence of dementia. For example, increases in social, mental and physical activity may be playing a role. Determining the causes of the decrease in incidence of dementia will help guide public health recommendations that may help further decrease the incidence of dementia.
Read the Neurology Today article, "Dementia Incidence Is Decreasing, Framingham Data Show," at http://bit.ly/NT-Framingham-dementia.
Jacqueline A. French, MD, FAAN, professor of neurology, New York University Comprehensive Epilepsy Center, New York, NY.
The Pick: Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: An open-label interventional trial. Lancet Neurol 2016; 15(3): 270-278.
The Findings: Placebo-controlled trials of cannabidiol (CBD) for Lennox-Gastaut and Dravet syndrome were positive, providing evidence that the drug is effective for reducing seizures in several severe epilepsy syndromes, after open label studies were suggestive.
Why It's Important: Patients frequently ask neurologists whether they should use medical marijuana or its derivatives as an epilepsy treatment. Many states now have compassionate programs. This data is the first evidence from rigorous trials that at least one component of cannabis has anticonvulsant properties, and outlines both the risks and potential benefits. If CBD is approved by the FDA, it will be rescheduled. CBD is currently schedule 1 (no medical benefit and high potential for abuse). Rescheduling will make research much easier. Future studies may continue to expand the conditions for which CBD can be efficacious.
Read the Neurology Today article, "Cannabidiol for Intractable Epilepsy: Promising Open-label Results Increase Interest in Forthcoming Blinded Trials," at http://bit.ly/NT-cannabidiol-epilepsy.
The Pick: French JA, Lawson JA, Yapici C, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2016; 388(10056): 2153- 2163.
The Findings: Between July 3, 2013 and May 29, 2015, 366 patients were enrolled and randomly assigned to placebo (n=119), low-exposure everolimus (n=117), or high-exposure everolimus (n=130). The response rate was 15.1 percent with placebo (95% CI 9.2–22.8; 18 patients) compared with 28·2% for low-exposure everolimus (95% CI 20.3–37.3; 33 patients; p=0.0077) and 40.0 percent for high-exposure everolimus (95% CI 31.5–49.0; 52 patients; p<0.0001). The median percentage reduction in seizure frequency was 14·9% (95% CI 0.1–21.7) with placebo versus 29.3 percent with low-exposure everolimus (95% CI 18.8–41.9; p=0.0028) and 39.6 percent with high-exposure everolimus (95% CI 35.0–48.7; p<0.0001). Grade 3 or 4 adverse events occurred in 13 (11 percent) patients in the placebo group, 21 (18%) in the low-exposure group, and 31 (24 percent) in the high-exposure group. Serious adverse events were reported in three (3 percent) patients who received placebo, 16 (14 percent) who received low-exposure everolimus, and 18 (14 percent) who received high-exposure everolimus. Adverse events led to treatment discontinuation in two (2 percent) patients in the placebo group versus six (5 percent) in the low-exposure group and four (3 percent) in the high-exposure group.
Why It's Important: This is the first drug used for treatment of epileptic seizures that acts on the underlying defect leading to seizures (which in tuberous sclerosis is an overactivation of the MTOR pathway) rather than just acting non-specifically on seizures. The MTOR pathway has also been implicated in other causes of epilepsy such as cortical dysplasias.
Read the Neurology Today article, "Adjunctive Everolimus Therapy Found to Reduce Seizures in Tuberous Sclerosis Complex," at http://bit.ly/NT-everolimus.
Andrew S. Feigin, MD, associate professor of neurology and molecular medicine at Hofstra Northwell School of Medicine, Manhasset, NY.
The Pick: Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 2016;375(8):730-739.
The Findings: Essential tremor (ET) is a common and sometimes disabling movement disorder that often does not respond to medical therapy. This double-blind randomized trial of magnetic resonance imaging (MRI)-guided focused ultrasound demonstrated a meaningful improvement in measurements of activities of daily living and quality of life, which lasted up to 12 months in the trial in patients with moderate to severe ET that had been unresponsive to at least two prior medications. The procedure was generally well tolerated – paresthesia/numbness and gait disturbance were common, but dissipated over time in most subjects.
Why It's Important: Approximately 50 percent of ET patients do not respond to currently available medications. This new procedure now offers a meaningful option for some of these patients. The US Food and Drug Administration (FDA) has approved this therapy for ET, and the treatment will likely become more widely available.
Read the Neurology Today article, "Focused Ultrasound Thalamotomy Is Found to Reduce Hand Tremor in Essential Tremor," at http://bit.ly/NT-focusedultrasound.
The Pick: Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 2016;167(6):1469-1480.
The Findings: This study demonstrates that the gastrointestinal (GI) microbiota has an impact on the severity of parkinsonism in an alpha-synuclein overexpression mouse model of Parkinson's disease (PD). In addition, the GI microbiota from PD patients, but not healthy controls, when transplanted to mice that overexpress alpha-synuclein, enhance the development of Parkinson's disease (PD) motor features.
Why It's Important: The etiology of PD is likely multifactorial, related to both environmental and genetic factors. This paper suggests a novel pathogenic mechanism for PD by which the gut microbiome may interact with genetic susceptibility to cause or exacerbate PD. Though this study was in an animal model and needs to be validated in PD patients, it suggests several testable hypotheses and could lead to novel therapies for PD.
John Corboy MD, FAAN, professor of neurology, University of Colorado School of Medicine, Aurora, CO.
The Pick: Tourbah A, Lebrun-Frenay C, Edan G, et al, for the MS-SPI study group. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study Mult Scler 2016;22(13):1719-1731.1.
The Findings: In a double-blind, placebo-controlled trial, MD1003 (high-dose biotin) achieved sustained reversal of multiple sclerosis (MS)-related disability in a subset of patients with progressive MS, and it was well tolerated.
Why It's Important: The study suggests the possibility of protecting neurons and oligodendrocytes from cell death in patients with progressive MS.
The Picks: Several papers, among the top scored abstracts from the Science Committee of the Congress of the European Committee for Treatment and Research in MS, held in London in September. These studies have not yet been published in peer-reviewed journals.
ECTRIMS Abstract P 1271: Piehl Fl, Kockum I, Khademi M, et al. High sensitivity measurement of neurofilament-light levels in plasma demonstrates a significant reduction in multiple sclerosis patients starting fingolimod.
The Findings: Neurofilament is a neuronal protein that is released upon cell injury into the cerebrospinal fluid and into the blood of patients. Neurofilament-light levels indicate that there is ongoing activity in the brain. The average level of the neurofilament-light chain fell from 20.35 pg/ML to 13.75 pg/ML in MS patients after 12 months of fingolimod therapy, and continued to drop to a level of 13.23 pg/mL at 24 months.
Why It's Important: The possible development of a blood biomarker of neuronal damage, neurofilament-light levels, would have many uses, including assisting in diagnosis and in determining severity of illness, as well as defining response to medications.
Read the Neurology Today article, "Neurofilament Blood Test Could Potentially Help Monitor MS Progression," at http://bit.ly/NT-neurofilament-MS.
The Pick: ECTRIMS Abstract P751: Sormani MP, Schiavetti I, Signori A, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis.
The Findings: In a pooled meta-analysis that included 15 clinical trials or series, about 67 percent of MS patients who underwent hematopoietic stem cell transplantation were estimated to have achieved a no-evidence-of-disease-activity state for at least five years.
Why It's Important: This meta-analysis of high-dose immunoablation and stem cell rescue studies showed benefit, especially in younger patients with active disease. And this will, hopefully, lead to an international controlled clinical trial comparing this approach to other highly effective therapies.
Read the Neurology Today article, "Meta-Analysis Shows Stem Cell Transplantation Halts MS Progression for At Least Five Years," at http://bit.ly/NT-stemcellMS.
James L. Bernat, MD, FAAN, Louis and Ruth Frank Professor of Neuroscience, professor of neurology and medicine, Geisel School of Medicine at Dartmouth and Dartmouth-Hitchcock Medical Center, Hanover, NH.
The Pick: Wang LH, Elliott MA, Henson LJ, et al. Death with dignity in Washington patients with amyotrophic lateral sclerosis. Neurology 2016;87:2117-2122.
The Findings: Since 2009 in Washington State, 39 patients with amyotrophic lateral sclerosis (ALS) requested "death with dignity" (physician-assisted suicide; physician-assisted death), which is a prescription for lethal medications on request in the setting of terminal illness. Seventy-seven percent of these patients thereafter swallowed the lethal medications and killed themselves. The average age of patients was 65, and there were no reported complications. The principal reason cited by the patients was loss of autonomy and dignity accompanied by the loss of ability to enjoy activities. These findings paralleled a similar group of 92 ALS patients in Oregon who also had requested physician-assisted death.
Why It's Important: With the continued increase in the number of states legalizing physician-assisted death, practicing neurologists are increasingly likely to encounter patients making this request. Neurologists practicing in jurisdictions in which physician-assisted death has been legalized must understand the stipulations of the law including their duties and rights, and be prepared to respond to such requests. Currently, all states that have legalized physician-assisted death (Oregon, Washington, Montana, Vermont, California, and Colorado) allow physicians who choose not to participate to decline. It is unclear from this report the extent to which the ALS patients had help from relatives of friends to swallow the medications. The intent of the law is self-administration, but although this point is mentioned in the law, the precise boundaries of assistance are not stipulated.
Kevin N. Sheth, MD, FAAN, chief, division of neurocritical care and emergency neurology, Yale New Haven Hospital, New Haven, CT.
The Pick: Hutchinson PJ, Kolias AG, Timofeev T, et al, for the RESCUEicp Trial Collaborators. N Engl J Med 2016; 375:1119-1130.
The Findings: At six months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative statethan medical care. The rates of moderate disability and good recovery were similar in the two groups.
Why It's Important: Increased intracranial pressure has been associated with poor outcomes for many years. The findings clearly establish a beneficial role for surgery for this condition where patients have had limited options. The study also highlights the need to further understand which processes lead to elevation and then what we need to do to target those underlying processes. We now have estimates about possible outcomes to present to patients when making these treatment decisions.
Read the Neurology Today article, "New Evidence to Support Decompressive Craniectomy for Reducing Intracranial Pressure in TBI," at http://bit.ly/NT-craniectomy.
Brent Fogel, MD, PhD, FAAN, assistant professor of neurology, David Geffen School of Medicine, University of California, Los Angeles, CA.
The Pick: Lek M, Karczewski KJ, Minikel EV, et al, for the Exome Aggregation Consortium. Analysis of protein-coding genetic variation in 60,706 humans. Nature 2016;536(7616):285-291.
The Findings: The ExAC (Exome Aggregation Consortium) database is a collection of shared data from deep sequencing of the exome, the 1-2 percent of the genome coding for protein, from over 60,000 individuals. Collectively, this provides a snapshot of the complexity of human genetic diversity with over 7.4 million rare coding variants. In this study, the authors comprehensively analyze these rare genetic changes to answer questions such as what types of variants are present and how frequently these changes occur, whether such changes arise more than once over time in different populations, and to identify genes that appear intolerant of variations predicted to disrupt their function, suggesting they may represent currently unrecognized genes important to human health.
Why It's Important: The ExAC database is an invaluable resource in the interpretation of diagnostic testing for neurogenetic disease. It provides an assessment of how frequently a variant occurs in the human population, greatly improving the ability to distinguish potential pathogenic mutations in Mendelian diseases from rare polymorphisms both within and across different ancestries. On the converse, it also can recognize variants previously thought to be mutations that are in fact common in many or even a few specific populations and therefore likely polymorphisms. Although they may not utilize this database directly, a neurologist ordering virtually any modern genetic or genomic test receives a report that utilizes data from this resource, providing more clinical useful substance than the dreaded term "variant of uncertain significance."
The Pick: Tabebordbar M, Zhu K, Cheng JK, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science 2016 ;351(6271):407-411.
Nelson CE, Hakim CH, Ousterout DG, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 20162;351(6271):403-407.
Long C, Amoasii L, Mireault AA, et al. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 2016; 351(6271):400-403.
The Findings: These three independent studies utilize the CRISPR/Cas9 system to perform somatic in vivo gene editing to correct the genetic defect in the dystrophin gene in a mouse model of Duchenne muscular dystrophy. All studies reported expression of functional dystrophin in skeletal and heart muscle and a partial correction of the disease phenotype.
Why It's Important: These studies collectively demonstrate the potential for using in vivo gene editing as a treatment for Duchenne muscular dystrophy, other muscle diseases, and possibly other neurogenetic diseases as well.
Read the Neurology Today article, "Gene Editing with CRISPR/Cas9 Corrects Mutation in Duchenne Muscular Dystrophy Model," at http://bit.ly/NT-geneeditingDMD.
Bruce H. Cohen, MD, FAAN, professor of pediatrics, Northeast Ohio Medical University, director, NeuroDevelopmental Science Center, Akron Children's Hospital, Akron, OH.
The Pick: Kang E, Wu J, Gutierrez NM, et al. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature 2016: 540(7632):270-275.
The Findings: The study authors were able to conduct a successful spindle body transfer technique for mitochondrial replacement therapy in ova of women with mitochondrial DNA (mtDNA) mutations whose children had Leigh syndrome and MELAS (mitochondrial encephalomyopathy, lacticic acidosis, and stroke-like episodes). In the process, they learned that the pairing of mothers and healthy donors whose mitochondrial genomes have similar non-coding sequences may be key to protecting the safety and effectiveness of mitochondrial replacement therapy, preventing residual pathogenic maternal mtDNA from repopulating the rescued embryo.
Why It's Important: The findings suggest a possible mechanism for bypassing disease in the offspring of mothers with pathogenic mtDNA mutations.
The Pick: Powers SW, Coffey CS, Chamberlin LA, et al, for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med 2016; Epub 2016 Oct 27.
The Findings: In this randomized trial of children and adolescents with migraine, the primary outcome measure (50 percent reduction in the number of headache days in comparison with the baseline) was no different in those receiving placebo, amitriptyline, or topiramate. This abstract, which was simultaneously published with full data in the New England Journal of Medicine, was selected as a top-scored abstract at the Child Neurology Society annual meeting in October.
Why It's Important: In children and adolescents with migraine, non-pharmacologic methods for headache treatment may be warranted. As stated by the author in a public presentation at the Child Neurology Society this year, it is the caring and intent to intervene that may be important and not the specific pharmacologic intervention.
Read the Neurology Today article, "Two Preventive Migraine Medications Found Not More Effective Than Placebo for Children," at http://bit.ly/NT-pediatricmigraine.
Anne Louise Oaklander, MD, PhD, FAAN, associate professor of neurology, Harvard Medical School, Boston, MA.
The Pick: Stock W, Diouf B, Crews KR, et al. An inherited genetic variant in CEP72 promoter predisposes to vincristine-induced peripheral neuropathy in adults with acute lymphoblastic leukemia. Clin Pharmacol Ther 2016. Epub 2016 Sept 12.
The Findings: Peripheral neuropathy was prospectively graded by National Cancer Institute criteria. CEP72 promoter genotype (rs924607) was determined using polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) genotyping. Frequency of the CEP72 T/T genotype was higher in cases (31 percent vs. 10 percent, p=0.0221) and the incidence of vincristine-induced neuropathy (grades 2-4) was significantly higher in patients homozygous for the CEP72 T/T genotype. Seventy-five percent of the 20 patients homozygous for the CEP72 T allele developed grade 2-4 neuropathy, compared to 44% of patients with the CEP72 CC or CT genotype (p=0.0221).
Why It's Important: Acquired polyneuropathies are common, with overall prevalence of 1.7 percent, and diagnostic testing is complex and costly. These advances will help neurology move beyond testing for single-gene Mendelian diseases such as Charcot-Marie Tooth and hereditary spastic paraplegia. Next generation whole-exome and whole-genome sequencing (whole exome sequencing/whole genome sequencing) and copy number analyses may eventually allow neurologists to detect people at high risk of developing neuropathy from medical diseases and potentially neurotoxic treatments. This may suggest new targets for therapy development, but most importantly – as is the case for stroke and dementia – neuropathy could become more preventable.
The Pick: Chesler AT, Szczot M, Bharucha-Goebel D, et al. The role of PIEZO2 in human mechanosensation. New Engl J Med 2016; 375 (14):1355-1364.
The Findings: Whole-exome sequencing analysis was conducted in two patients who had unique neuromuscular and skeletal symptoms, including progressive scoliosis, which did not conform to standard diagnostic classification. In vitro and messenger RNA assays, functional brain imaging, and psychophysical and kinematic tests were used to establish the effect of the genetic variants on protein function and somatosensation. Each patient carried compound-inactivating variants in PIEZO2, and each had a selective loss of discriminative touch perception but nevertheless responded to specific types of gentle mechanical stimulation on hairy skin. The patients had profoundly decreased proprioception leading to ataxia and dysmetria that were markedly worse in the absence of visual cues. However, they had the ability to perform a range of tasks, such as walking, talking, and writing, that are considered to rely heavily on proprioception.
Why It's Important: This examination at the National Institute of Neurological Disorders and Stroke (NINDS) of two unrelated youngsters with undiagnosed neuromuscular conditions revealed isolated losses of vibration detection, touch discrimination on glabrous skin, and joint proprioception. Whole exome sequencing identified different autosomal recessive loss-of-function variants in PIEZO2, which encodes a stretch-gated ion channel. Studies of knock-out mice and transfected cells corroborated the findings in patients. This is important because it identifies PIEZO2 as the major transducer of the sense of touch in humans. It not only establishes a new type of neuropathy, but may help explain why some of us are clumsy while others can put a wicked spin on a fastball.
Neil A. Busis, MD, FAAN, chief, division of neurology, University of Pittsburgh Medical Center-Shadyside, Pittsburgh, PA.
The Picks: Sinsky C, Colligan L, Li L, et al. Allocation of physician time in ambulatory practice: A time and motion Study in 4 Specialties. Ann Intern Med 2016;165(11):753-760. (Also selected by James L. Bernat, MD, FAAN)
Hingle S. Electronic Health Records: An unfulfilled promise and a call to action. Ann Intern Med 2016;165(11):818-819.
The Findings: Fifty-seven ambulatory care physicians in four specialties (family medicine, internal medicine, cardiology, orthopedics) in four states were directly observed for 430 hours; 21 physicians also completed after-hours diaries. Physicians' time spent on four activities was measured: direct clinical face time accounted for 27 percent; electronic health record and deskwork accounted for 49.2 percent; and administrative tasks and other tasks accounted for the remainder. In the exam room, physicians spent 52.9 percent of the time on direct clinical face time and 37 percent of the time on electronic health records and deskwork. They also spent 1-2 hours each night after office hours devoted primarily to electronic health records completion. The authors calculated that for every hour physicians spent in direct clinical face time with patients, they spent nearly an additional 2 hours on electronic health records and deskwork during the clinic day and 1-2 hours of personal time finishing up electronic health records and deskwork at night.
Why It's Important: It confirms what most clinicians already know, that EHR use adds considerable clerical burden to practice. But it goes beyond that in several important ways: It shows that measuring what physicians do is a more accurate assessment of physician work than retrospectively surveying what physicians do. It therefore questions the current basis of the relative value system. It also demonstrates that cognitive service work has changed considerably from when evaluation and management (E/M) services were originally valued at the beginning of the use of the resource-based relative value scale, and that current E/M services are probably undervalued. By extension, it suggests that these services and all others (including surgical services) should be re-evaluated by time and motion studies if they are to be valued fairly. Finally, the study authors found that physicians who use EHRs and computerized physician order entry have decreased satisfaction and a higher risk for professional burnout. Physicians who burn out are at a significantly greater risk for depression and suicidal ideation, and there is also concern that they are more likely than satisfied colleagues to provide lower-quality patient care and to leave clinical practice early. Thus, government mandates to use EHRs contribute to physician burnout, which will impede care for neurologic patients. For many years, when we advocated at the Centers for Medicare and Medicaid Services, we were told they were not interested in listening to our complaints about their policies until we can demonstrate that their policies will adversely affect their beneficiaries by decreasing access to care. This provides that missing link.
Dr. Bernat adds: Physician burnout has many causes but one is physicians' requirements to conduct meaningless tasks, particularly when doing so sacrifices time that should be devoted to proper patient care. The extra time that physicians are now required to devote to completing electronic health records has been shown to correlate with the rate of physician burnout. All practicing physicians are aware of this added time demand but this study quantifies its huge burden on physicians. An important intervention to reduce physician burnout must be to reduce this unreasonable additional time demand
James C. Grotta, MD, FAAN, director of stroke research and the mobile stroke program at the Memorial Hermann Hospital, Houston, TX.
The Pick: Kernan WN, Vicoli CM, Furie KL, et al, for the IRIS Trial Investigators. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016; 374:1321-1331.
The Findings: Pioglitizone reduced the risk of subsequent stroke in a large prospective placebo controlled trial in non-diabetic patients with insulin resistance who had suffered a transient ischemic attack (TIA) or stroke.
Why It's Important: After TIA or stroke, neurologists should consider testing their non-diabetic patients for insulin resistance and treating them with pioglitazone.
Read the Neurology Today article, "Pioglitazone Found to Be Associated with a Lower Risk of Secondary Stroke in Non-Diabetic Patients with Insulin Resistance," at http://bit.ly/NT-pioglitazone.
The Pick: Qureshi A, Palesch YY, Barsan WG, et al, for the ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Engl J Med 2016; 375:1033-1043.
The Findings: Patients with intracerebral hemorrhage (ICH) were randomly assigned to conventional blood-pressure lowering (SBP 140-179) or intensive blood-pressure lowering [systolic blood pressure (SBP) 110-139] within 4.5 hours of symptom onset. No benefit on outcome was observed.
Why It's Important: A previous study (INTERACT2) reported in 2013 in the New England Journal of Medicine had shown a non-significant improvement in outcome with early reduction of blood pressure after ICH. The combined results of the two studies suggest that SBP >180 should be acutely treated after ICH, but that aggressive reduction to SBP <140 is not necessary.
Read the Neurology Today article, "Intensive Treatment No Better Than Standard Treatment for Lowering Blood Pressure in People with Acute Intracerebral Hemorrhage," at http://bit.ly/NT-intensiveBP.
The Pick: Johnston SC, Amarenco P, Albers GW, et al, for the SOCRATES Steering Committee and Investigators. Ticagrelor versus aspirin in acute stroke or transient ischemic Attack. N Engl J Med 2016; 375:35-43.
The Findings: Patients with non-cardioembolic TIA or stroke were randomized to ticagrelor or aspirin in a large prospective international study. There was no increased bleeding with ticagrelor. While ticagrelor did not reduce the incidence of the primary combined endpoint of stroke, myocardial infarction, or vascular death (6.7 percent vs 7.5 percent with ticagrelor vs aspirin respectively, p=.07), ticagrelor did decrease the incidence of stroke, which was a secondary endpoint (5.8 percent vs 6.7 percent, p=.046).
Why It's Important: Ticagrelor does not increase bleeding when used for secondary stroke prevention, and while not superior to aspirin, it may be an alternative in certain patients and is worth further study.
Read the Neurology Today article, "Ticagrelor Found Not Superior to Aspirin for Secondary Stroke Prevention," at http://bit.ly/NT-ticagrelor.
The Pick: Anderson CS, Robinson T, Lindley RI, et al, for the ENCHANTED Investigators and Coordinators. Low-dose versus standard-dose intravenous alteplase in acute ischemic stroke. N Engl J Med 2016; 374:2313-2323.
The Findings: Patients with acute stroke who were eligible for tissue plasminogen activator (tPA) using standard criteria were randomized to a full dose or reduced dose (0.6 mg/kg with 15 percent given as a bolus) of tPA. Sixty-three percent of patients were Asian. The study was designed as an inferiority study. Death or disability occurred in 53.2 percent of reduced dose and 51.1 percent of standard dose patients (p=0.51 for non-inferiority). Major symptomatic intracranial hemorrhage occurred in 1 percent of reduced dose vs 2.1 percent of standard dose patients (p=0.01). There was no heterogeneity in results among the different ethnic groups included in the study.
Why It's Important: Bleeding after tPA is the most feared complication and lower doses of the drug are often given to Asians who have smaller body mass. While not proven to be as effective as full dose tPA in this study, lower dose tPA may be safer. Further study of lower doses in patients at highest risk for bleeding complications would seem to be indicated by this finding.
Read the Neurology Today article, "New Reason to Question Treating Asians for Ischemic Stroke with Low-Dose tPA," at http://bit.ly/NT-TPAdose.
Vladimir Hachinski, MD, FAAN, professor of neurology, University of Western Toronto, London, Ontario.
The Pick: Iturria-Medina Y, Sotero RC, Toussaint PI, et al, for the Alzheimer's Disease Neuroimaging Initiative. Is Alzheimer a vascular disease? Early role of vascular dysregulation of late-onset Alzheimer's disease based on multifactorial data-driven analysis. Nature Commun 2016; 7: 11934.
The Findings: The authors analyzed 7,700 brain images, plasma, and cerebrospinal biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Through a multifactorial data-driven analysis they found that vascular dysregulation is an early pathological event that leads to late-onset Alzheimer's disease.
Why It's Important: Instead of rounding up the usual suspects that are implicated in Alzheimer's disease (amyloid-beta and tau deposition), the study authors took a hypothesis-free approach and let the data drive the results. It is tempting to conclude that the decreased blood flow suggests ischemia and that Alzheimer's is a vascular disease. However, the decreased blood flow may be secondary to decreased metabolic demand. Either or both ways, this study opens the door to new approaches in preventing, mitigating, or delaying dementia.
Read the Neurology Today article, "Large Dataset Spots Vascular Dysregulation as First Event in Alzheimer's Pathology," at http://bit.ly/NT-vasculardysregulation.
This story will appear in print in the January 19 issue.