Article In Brief
The Neurology Today editorial board highlights the advances that occurred in 2022 in multiple subspecialties and areas of practice.
At the end of each year, we ask our editorial board to highlight advances and developments that changed neurology and/or their subspecialty in some way. It might be a study that offered new clinical insight or perspective on a therapy or a new policy that informed their subspecialty. The recommendations for 2022 hew true to this theme. No matter the challenges—and as the so-called public health emergency associated with COVID-19 began to fade—neurology as a field continued to grow.
Read on for the Neurology Today editorial board top picks for the news, events, and ideas that mattered and moved the field forward this past year.
ADVANCED PRACTICE PRACTIONERS
JULIE A. GURWELL, PHD, PA-C
Professor of Neurology, Director of Advanced Practice Providers
University of Kentucky
The Pick: Harrison DS, Naclerio N, Swider K, et al. Education research: Neurologic education in physician assistant programs https://ne.neurology.org/content/2/1/e200029. Neurology Education 2022; Epub 2022 Dec 1.
The Findings: The study reviews the neuroscience topics covered in programs for physician assistants (PA) based on data gathered from surveyed PA program directors and content reviews of websites of accredited PA programs. The completion rate of the survey was 23.5 percent, and 43.3 percent of programs reported providing a dedicated neuroscience course. Core neuroscience components included instruction in neuroanatomy, neuropharmacology, neurophysiology, neurologic diseases, and a neurologic exam in at least 90 percent of programs. Neuropathology and neuroradiology were included in fewer curricula. In clinical training, only one program reported having a required neurology rotation, and 51 programs offered an elective neurology rotation. Of the programs surveyed, 42 stated that, on average, one graduate will pursue clinical practice in neurology.
Why It's Important: This study underscores the dearth of clinical neurology opportunities and didactic exposure in neurology for APPs in clinical training. Advanced practice practitioners (APPs) can be used in neurology practices to increase patient access, but as this paper suggests, APP graduates interested in careers in neurology require further training and course work to prepare them adequately for patient care responsibilities. The number of neurology APP residency/fellowship programs are increasing in the US, with expectations of bridging the gap between fundamental and advanced neurologic care, knowledge, and clinical skills.
JAMES C. GROTTA, MD, FAAN
Director of Stroke Research and Mobile Stroke Unit
Memorial Hermann-Texas Medical Center Houston, TX
The Picks: Tao C, Nogueira RG, Zhu J, et al. Trial of endovascular treatment of acute basilar artery occlusion. N Engl J Med 2022;387:1361-1371
Jovin TC, Li C, Wu L, et al, Trial of thrombectomy 6-24 hours after stroke due to basilar artery occlusion. N Eng J Med 2022;387:1373-84
The Findings: Two randomized trials from China in patients with acute basilar artery occlusion treated with endovascular thrombectomy within 24 hours of onset versus best medical management (the control group) showed an absolute reduction in mortality of 18 percent and 11 percent, respectively. Forty-six percent of those treated with the intervention had more frequent independent or semi-independent 90-day outcomes (modified Rankin score 0-3) compared with 23 to 24 percent of the control group.
Why It's Important: Occlusion of the basilar artery results in death or severe disability in approximately 80 percent of patients, and to date, no treatment has had a substantial impact on improving its devastating impact. Endovascular thrombectomy is a powerfully effective treatment for anterior circulation large vessel occlusions but has not been effectively studied for basilar occlusion. These two studies show that we now have an effective treatment for this stroke type with the most devastating outcome, and they provide guidance for appropriate selection of patients.
The Picks: Hack RJ, Rutten J, Lesnik Oberstein S. What's in a domain? The role of NOTCH3 EGFr domains in CADASIL disease severity https://n.neurology.org/content/99/5/179. Neurology 2022. Epub 2022 Aug 1.
Hack RJ, Cerfontaine MN, Gravesteijn G, et al. Effect of NOTCH3nEGFr group, sex, and cardiovascular risk factors on CADASIL clinical and neuroimaging outcomes https://www.ahajournals.org/doi/10.1161/STROKEAHA.122.039325. Stroke 2022;53:3133-3144.
Cho BPH, Harshfield EL, Al-Thani M, et al. Association of vascular risk factors and genetic factors with penetrance of variants causing monogenic stroke https://jamanetwork.com/journals/jamaneurology/fullarticle/2797931. JAMA Neurol 2022;79(12):1303-1311.
The Findings: A study and editorial by RJ Hack, et al, highlighted that variants in the epidermal growth factor—like repeat (EGFr) domain of the NOTCH3 protein—determine the severity of CADASIL (cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy). Variants in the EGFr 1-6 domain are the most important determinant of age at first stroke, white matter hyperintensity volume, and other relevant imaging markers, and they are more important than sex, hypertension, diabetes, and smoking. On the other hand, variants in the 7-34 positions may be associated with less severe disease and may be clinically and radiographically indistinguishable from other causes of small vessel disease in elderly patients. The study by Cho, et al, showed that cardiovascular risk factors significantly influence the incidence of stroke in these patients.
Why It's Important: Patients with the NOTCH3 protein cysteine mutation are diagnosed with CADASIL, which typically is associated with premature stroke and dementia. However, with more frequent genetic testing and imaging, we are recognizing that NOTCH3 cysteine mutations are more common than previously thought in the general population (1:300 to 500), and that there is substantial heterogeneity in clinical phenotype. These studies of EGFr domain variability are useful for patient counseling and also may provide a clue to the etiology of otherwise unexplained small vessel disease diagnosed in aging patients. Furthermore, rigorous control of associated cardiovascular risk factors may slow the development of clinical manifestations of CADASIL.
The Pick: Menon BK, Buck BH, Singh N, et al, for the AcT Trial Investigators. Intravenous tenecteplase compared with alteplase for acute ischemic stroke in Canada (AcT): A pragmatic, multicenter, open-label, registry-linked, randomized, controlled, non-inferiority trial https://www.thelancet.com/article/S0140-6736(22)01054-6/fulltext. Lancet 2022;400(10347):161-169.
The Findings: This large nationwide study comparing established treatment with intravenous alteplase (tPA) (standard dose 0.9 mg/kg) with tenecteplase (TNK) (0.25 mg/kg) found no difference in the rate of good outcomes (35 percent vs. 37 percent, respectively), symptomatic hemorrhage (3 percent for both groups), or mortality (15 percent for both groups) at 90 days. Results with TNK fell within the pre-established non-inferiority boundaries.
Why It's Important: TNK has greater fibrin specificity and longer half-life than tPA. Consequently, it may be more convenient since it does not require a post-bolus infusion. Previous studies comparing these two treatments have been inconclusive but have established 0.25 mg/kg as the preferred TNK dose. This large, well-conducted study convincingly shows that TNK is “as good” as tPA and a “reasonable alternative.”
While the study did not show superiority of TNK over tPA, its equivalence will support its increased use because of its greater convenience. This would be particularly advantageous in “drip and ship” scenarios.
ANN TILTON, MD, FAAN
Professor of Neurology and Pediatrics
Louisiana State University Health Sciences Center
New Orleans, LA
The Pick: Amlie-Lefond. Pediatric stroke—Are we asking the right questions? The 2022 Sidney Carter award lecture https://n.neurology.org/content/early/2022/11/08/WNL.0000000000201487. Neurology 2022; Epub 2022 Nov 8.
The Findings: In this invited article, the author who presented the Sidney Carter award lecture at the 2022 AAN Annual Meeting pointed out that while research on adult stroke abounds, studies on stroke in children are lacking. Additionally, the information on adult stroke cannot be extrapolated to the pediatric patient, where the etiologies and developmental impact are unique.
Why It's Important: This article is a call for support for research in pediatric stroke and emphasizes that focusing on the unique neurodevelopmental impact is essential.
The Pick: Majzner RG, Ramakrishna S, Yeom KW, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas https://www.nature.com/articles/s41586-022-04489-4. Nature 2022;603(7903):934-941.
The Findings: Children with diffuse H3K27M-mutated midline brain stem and spinal cord gliomas uniformly have a fatal prognosis. Radiotherapy is the only modality that has been shown in studies to be a therapeutic option, but there is a significant need for other treatment approaches. This article provides promising data on the use of immunotherapy. The authors have previously demonstrated promising preclinical efficacy of GD2-directed chimeric antigen receptor (CAR) T cells, providing the rationale for a first-in-human phase I clinical trial (NCT04196413). Three of the four initial patients showed positive responses as well as the expected side effects. We know that CAR T cell therapy has significant risk for toxicities that have the potential to dramatically affect this vulnerable neuroanatomic area. However, with aggressive management of the side effects, this treatment may offer an alternative in a disease with minimal options.
Why It's Important: This phase 1 trial provides some optimism for a potential treatment option for patients with these aggressive and lethal tumors. The authors also share detailed information on the therapeutic approach in these select patients.
CLINICAL ETHICS/NEUROCRITICAL CARE
MICHAEL A. RUBIN, MD, MA, FAAN
Associate Professor of Neurology and Neurosurgery
UT Southwestern Medical Center Peter J. O'Donnell Jr. Brain Institute
The Pick: Derse AR. The physician-patient relationship https://www.nejm.org/doi/full/10.1056/NEJMp2201630. N Engl J Med 2022;387(8):669-672.
The Findings: This article reviews the development of consent and shared decision making in the physician-patient relationship and how that relationship has been influenced by misinformation, contemporary emphasis on self-determination, and COVID-19.
Why It's Important: This piece demonstrates that regardless of other social developments, we have a duty to advocate for the patient's physical well-being.
The Pick: Lewis A. The uniform determination of death act is being revised https://link.springer.com/article/10.1007/s12028-021-01439-2. Neurocrit Care 2022; 36(2):335-338.
The Findings: The Uniform Determination of Death Act creates the framework for how we determine brain death in the United States. Legal challenges and controversy about that framework have garnered more attention, with misinformation and politics adding confusion to this fundamental issue.
Why It's Important: Our approach to death and organ recovery may undergo significant changes in coming years as a result of this process.
ERIC M. MCDADE, DO
Professor of Neurology
Washington University at St. Louis School of Medicine
St. Louis, MO
The Pick: van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease https://www.nejm.org/doi/10.1056/NEJMoa2212948. N Engl J Med 2022; Epub 2022 Nov 29.
The Findings: The results of the phase 3 study of lecanemab for mild Alzheimer's disease demonstrated an approximately 30 percent slowing in the change of the Clinical Dementia Rating box score between the treated and placebo group over an 18-month period of time. Lecanemab is an anti-amyloid beta immunotherapy that had demonstrated in phase 2 studies substantial amyloid plaque reduction on PET. In this phase 3 study, the primary outcome and all key, clinical, secondary outcomes demonstrated a statistically significant difference between the treatment group and placebo.
Why It's Important: The role of amyloid reduction for disease modification of symptomatic Alzheimer's disease remains uncertain. The results of the CLARITY-AD study with lecanemab have provided some of the clearest and consistent effects of what dramatic amyloid reduction can achieve. Although the differences in the groups was relatively modest, there were suggestions of an increase in benefit with longer exposure. Long-term exposure studies will be needed to demonstrate whether lecanemab continues to improve symptoms over time and if so, this study will mark the beginning of new treatment paradigm in Alzheimer's disease.
Dr. McDade disclosed that he has institutional grants from Eisai for lecanemab and E2814 and was a recent co-author with employees of Eisai for phase 2 data from lecanemab.
The Pick: Lee M, Whitsel E, Avery C, et al. Variation in population attributable fraction of dementia associated with potentially modifiable risk factors by race and ethnicity in the US https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793916. JAMA Netw Open 2022;5(7):e2219672.
The Findings: This cross-sectional study found that 41 percent of dementia cases were associated with 12 potentially modifiable risk factors. The study focused on a US based population and included an analysis of African American, Hispanic, non-Hispanic White, and non-Hispanic Asian populations. Across all populations, midlife obesity, sedentary lifestyle, and hypertension consistently accounted for the greatest risk of dementia, with evidence of a greater prevalence, and subsequent risk, in African American and Hispanic populations.
Why It's Important: This study strongly supports a recent report from the Lancet Commission that attributes approximately 40 percent of the risk of lifetime dementia to preventable factors. There remains little doubt that a limited number of highly preventable factors are important to reducing dementia risk. The prevention of dementia remains the greatest opportunity for meaningful reduction of the burden of the disease. Although the development of disease-related biomarkers and disease-modifying therapies for diseases like Alzheimer's provide optimism, it is likely that these developments will still be limited in their scope. Thus, lifestyle approaches remain the best opportunity for broad-scale reduction of risk for dementia. Studies like this strongly support the need for policies to address these risk factors.
The Pick: Kim C, Haldiman T, Kang SG, et al. Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease https://www.science.org/doi/10.1126/scitranslmed.abg0253. Sci Transl Med 2022;14(626):eabg0253.
The Findings: Clinical heterogeneity in neurodegeneration in Alzheimer's disease and related dementias is well known, but the causes remain poorly understood. In this publication, the investigators used post-mortem brain samples from individuals with pathology confirmed, rapidly progressive Alzheimer's disease. Specifically, they focused on the tau isolated from the hippocampus of rapidly progressive AD cases and those with a typical duration and found that in rapidly progressive forms there were unique conformations of tau with a greater ability to “seed’ new tau tangles.
Why It's Important: There has been a rapid development in the ability to measure tau-related biomarkers in AD. If the work by these researchers is replicated, it is possible that measures of potentially more “toxic” forms of tau proteins could be identified as a way of better predicting those with a risk of faster progression.
JACQUELINE A. FRENCH, MD, FAAN
Professor of Neurology
NYU Grossman School of Medicine
Chief Medical and Innovation Officer, Epilepsy Foundation
New York, NY
The Pick: The first epilepsy patient was implanted with inhibitory cell therapy and followed for three months. https://bit.ly/3jol5qg. Accessed Dec. 23, 2022.
The Findings: Neurona Therapeutics sponsored a phase I/2 trial to implant inhibitory cell therapy—a single infusion of NRTX-1001 cells derived from human pluripotent stem cells—into patients with epilepsy. The neuronal cells locally secrete gamma-aminobutyric acid (GABA) into the hippocampus. Two subjects have successfully been implanted to date in this ongoing trial. So far, this therapy is very preliminary. The study primarily assesses safety and cell viability. The first subject did well at a three month follow-up and reportedly went from 30-plus seizures per month to only four during those three months.
Why It's Important: For almost a decade, the epilepsy field has contemplated true disease-modifying therapy for the condition. In 2022, a number of gene therapy and gene-modifying (antisense oligonucleotide) trials were underway for rare genetic epilepsies. But now, with this trial, disease-modifying therapies also are moving forward for focal epilepsies. The hope is that this therapy will behave like a permanently implanted GABA factory so the recipient would not need to remember to take this medication on a daily basis, which can be a major burden to people with epilepsy. So far, only people with a focus in the right temporal lobe have been implanted, meaning that if any negative consequence occurs, the tissue can safely be resected. While still in its early days, this trial may represent the beginning of a new era in epilepsy therapy.
The Pick: Sisterson ND, Kokkinos V, Urban A, et al. Responsive neurostimulation of the thalamus improves seizure control in idiopathic generalized epilepsy: Initial case series https://journals.lww.com/neurosurgery/Abstract/2020/11000/Responsive_Neurostimulation_of_the_Thalamus.42.aspx. J Neurol Neurosurg Psychiatry 2022;93(5):491-498.
Yang JC, Bullinger KL, Isbaine F, et al. Centromedian thalamic deep brain stimulation for drug-resistant epilepsy: single-center experience https://thejns.org/view/journals/j-neurosurg/137/6/article-p1591.xml. J Neurosurg 2022;137(6):1591-1600.
Dalic LJ, Warren AEL, Bulluss KJ, et al. DBS of thalamic centromedian nucleus for Lennox-Gastaut syndrome (ESTEL Trial) https://onlinelibrary.wiley.com/doi/full/10.1002/ana.26280. Ann Neurol 2022;91(2):253-267.
The Findings: Several publications in 2022 focused on stimulation of the thalamus for generalized epilepsy. One case series described outcomes in 14 patients with both idiopathic generalized epilepsy (IGE) and other generalized and bifrontal epilepsies stimulated in the centromedian nucleus (CMN) of the thalamus. The other case series described outcomes in four patients with IGE stimulated in various thalamic locations; thalamic stimulation provided excellent seizure benefit to most patients. A small, double-blind, randomized trial of continuous CMN stimulation in patients with Lennox-Gastaut syndrome failed to find a statistical difference in proportion of subjects with a 50 percent reduction on seizures—50 percent active vs. 22 percent sham (adjusted OR=3.1, 95percent CI=0.44 to 21.45, p=0.25)—but several secondary measures were positive, including reduction of electrographic seizures on ambulatory EEG. One infection led to device removal.
Why It's Important: In the last decade, two brain neuromodulator stimulation devices have been approved for the treatment of focal epilepsy—responsive neurostimulatory (RNS) from Neuropace in 2014 and deep brain stimulation (DBS) from Medtronic in 2018. But there also has been interest in treating generalized epilepsy, including IGE and combined focal/generalized epilepsies such as Lennox-Gastaut syndrome. The studies to date have been small and uncontrolled. Now, in addition to the randomized trial of CMN stimulation for Lennox-Gastaut, Neuropace has initiated a prospective, multicenter, single-blind, randomized, sham stimulation-controlled pivotal study of thalamic stimulation in IGE. Hopefully we can eventually expand the population that can benefit from brain neuromodulatory stimulation.
HEADACHE MEDICINE AND CONCUSSION
AMAAL STARLING, MD
Associate Professor of Neurology
The Pick: Schwedt TJ, Hentz JG, Sahai-Srivastava S, et al, for the MOTS Investigators. Patient-centered treatment of chronic migraine with medication overuse: A prospective, randomized, pragmatic clinical trial https://n.neurology.org/content/98/14/e1409. Neurology 2022;98(14):e1409-e1421.
The Findings: This open-label, pragmatic clinical trial randomized adult participants with chronic migraine with medication overuse to a migraine preventive, either switching to an alternative acute therapy with strict limits (less than two treatment days per week) or continuing the overused medication without limits. The primary outcome was the frequency of moderate-to-severe headache days during weeks nine to 12. Migraine preventive medication—without switching the overuse medication or limiting the overused medication—was not inferior to preventive medication with switching and limiting symptomatic medication.
Why It's Important: The management of chronic migraine with medication overuse lhas been long debated in the field. Many clinicians require patients to strictly discontinue their overuse acute medications prior to the initiation of preventive medications. The suggestion was that preventive options may not be effective in the setting of medication overuse. This often resulted in increased pain, poor adherence, and frequent relapse. This evidence highlights the importance of initiating prevention for the reduction of moderate-to-severe headache day frequency regardless of switching or not switching the overused acute medication. With this evidence in hand, clinicians can engage in shared decision-making with each individual patient.
MELISSA J. NIRENBERG, MD, PHD, FAAN
Professor of Neurology Icahn School of Medicine at Mount Sinai New York, NY
The Pick: Schrag S-E, Martino D, Wang H, et al, on behalf of European Multicentre Tics in Children Study (EMTICS). Lack of association of group A streptococcal infections and onset of tics: European multicenter tics in children study https://n.neurology.org/content/98/11/e1175. Neurology 2022; Epub 2022 Feb 2.
The Findings: In this well-designed prospective, multicenter study, the authors evaluated the potential relationship between streptococcal infection and tic disorders in children ages 3 to 10 years old with a family history of chronic tics. The results provide compelling evidence that streptococcal infection is not associated with new-onset tic disorders in these patients.
Why It's Important: These findings provide evidence that anti-streptococcal antibiotics should not be used to treat childhood-onset tic disorders in this population. This should lead to reduced use of unnecessary antibiotics in tic disorders.
The Pick: Cramer SW, Do TH, Palzer EF, et al. Persistent racial disparities in deep brain stimulation for Parkinson's disease https://onlinelibrary.wiley.com/doi/full/10.1002/ana.26378. Ann Neurol 2022;92:246-254.
The Findings: These study authors used database analysis to show that Black people with Parkinson's disease (PD) were five times less likely to pursue deep brain stimulation (DBS) than White people with PD, even after adjusting for factors such as sex, age, private insurance status, and number of comorbidities. They concluded that racial disparities in DBS use have not significantly changed since the first 10 years when DBS first became available for treatment of PD, even as the overall use of DBS has increased.
Why It's Important: The findings raise awareness of health care disparities in the management of PD, highlighting the need for further investigation of the underlying causes of these gaps and how to address them. While the authors frame this as “underutilization” of DBS in Black people with PD versus White people with PD, it should be noted that clinical trials of DBS also have included very few Black people. Thus, it is not known whether risks and benefits observed in clinical trials can be generalized to the Black population.
The Pick: Hopfner F, Tietz A, Ruf VC, et al. Common variants near ZIC1 and ZIC4 in autopsy-confirmed multiple system atrophy https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.29164. Mov Disord 2022; Epub 2022 Aug 23.
The Findings: Multiple system atrophy (MSA) is a rare neurodegenerative disorder for which it has been difficult to identify underlying genetic causes. In this genome-wide association study of 731 autopsy-confirmed cases of MSA, the authors identified a locus associated with MSA on chromosome 3, near the genes that encode the zinc finger proteins of cerebellum 1 (ZIC1) and 4 (ZIC4). They then used immunocytochemistry to show that ZIC4-immunoreactive cerebellar neurons were significantly reduced in the cerebellar variant of MSA (MSA-C) versus the parkinsonian variant of MSA (MSA-P) and controls. ZIC4 and ZIC1 mutations previously have been shown to cause developmental cerebellar disorders; antibodies against ZIC4 also are known to cause paraneoplastic cerebellar ataxia.
Why It's Important: These findings, if confirmed, have identified a potential genetic risk factor for MSA that may link together the cerebellar variant of MSA with known developmental and paraneoplastic cerebellar disorders.
STEPHEN KRIEGER, MD, FAAN
Professor of Neurology
Icahn School of Medicine at Mount Sinai
New York, NY
The Picks: Kuhlmann T, Moccia M, Coetzee T, et al. Multiple sclerosis progression: Time for a new mechanism-driven framework https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00289-7/fulltext. Lancet Neurol 2022; Epub 2022 Nov 18.
Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability https://academic.oup.com/brain/article/145/9/3147/6519354. Brain 2022;145(9):3147-3161.
The Findings: These papers reflect a major shift in the thinking about the clinical course of multiple sclerosis (MS) from one comprising distinct phenotypes—relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS —to a more unified and biologically defined disease continuum. Specifically, the concept that “progression” begins early in the disease rather than as a late phenomenon underscores much of the current research into MS pathogenesis and treatment.
The Kuhlmann paper outlines this shift to a more mechanistic approach to understanding drivers of MS disease course and progressive prognosis and paves the way for further studies to explicate these pathologic mechanisms. The Lublin paper builds on his existing RRMS and SPMS phenotype dichotomy by using a large clinical trial dataset to parse out that disability in MS can be accumulated in two fundamental ways: through relapses (relapse-associated worsening, or RAW) and as progression independent of relapse activity (PIRA). “Our data confirm that relapses contribute to the accumulation of disability, primarily early in multiple sclerosis,” Dr. Lublin and colleagues wrote. “PIRA begins in relapsing-remitting multiple sclerosis and becomes the dominant driver of disability accumulation as the disease evolves.”
Why It's Important: By recognizing that these two drivers of disability accumulation—RAW and PIRA—may occur contemporaneously, a more individualized approach to MS disease course can be achieved. The evolution in our field that these papers demonstrated nicely aligns with the topographical model of conceptualizing MS disease course that I've worked on for several years. Using this approach, disability in MS can be shown to occur through the development of new lesions that cross the clinical threshold as relapses, or through the gradual loss of reserve that unmasks deficits from clinically silent lesions, blurring the distinctions between phenotypes when they occur contemporaneously. Further identifying the mechanistic drivers of the loss of reserve will be essential moving forward.
“The apparent evolution to a progressive course reflects a partial shift from predominantly localized acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination,” Kuhlmann and colleagues wrote.
The Picks: Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis https://www.science.org/doi/10.1126/science.abj8222. Science 2022;375(6578):296-301.
Robinson WH, Steinman L. Epstein-Barr virus and multiple sclerosis https://www.science.org/doi/10.1126/science.abj8222. Science 2022;375(6578):264-265.
The Findings: Arguably the most visible publication in the field of MS for the last several years (with an Altmetric score topping 11,000), this work from the laboratory of Alberto Ascherio, MD, and colleagues provided the strongest data to date that Epstein-Barr virus (EBV) infection is causal for the development of MS. Using a large retrospective database, they found that EBV infection portends a 32-times increase in risk of subsequent MS diagnosis. Furthermore, of nearly 1,000 MS cases reviewed, virtually all of them were positive for EBV.
Why It's Important: While the association between MS and EBV has been long recognized, the sequential, causal chain has never been more clearly elucidated than in this work. In their commentary, the editorialists stated: “Infection with EBV is likely to be necessary, but not sufficient, to trigger development of MS. Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”
The paper in Science has indeed already ignited a series of mechanistic studies looking to further untangle the mechanistic relationship between EBV and MS development, a path of inquiry likely to lead to the development of entirely new therapeutic approaches—modalities that relate to EBV infection and the cells in the immune system that are influenced to cause central nervous system-targeted autoimmunity and demyelination.
SACHIN AGARWAL, MD, MPH
Associate Professor of Neurocritical Care
Columbia University Irving Medical Center
New York, NY
The Pick: Garcia RA, Spertus JA, Girotra S, et al. Racial and ethnic differences in bystander CPR for witnessed cardiac arrest https://www.nejm.org/doi/pdf/10.1056/NEJMoa2200798. N Engl J Med 2022;387(17):1569-1578.
The Findings: In an analysis of 10,054 witnessed out-of-hospital cardiac arrests from 2013 through 2019 within CARES (Cardiac Arrest Registry to Enhance Survival), there were large differences in the incidence of bystander cardiopulmonary resuscitation (CPR) by race and ethnicity for witnessed out-of-hospital cardiac arrest. The relative likelihood of receiving bystander CPR at home was 26 percent lower for Black and Hispanic persons than for White persons, and the likelihood of bystander CPR for arrests in public locations was 37 percent lower for Black and Hispanic persons.
Why It's Important: Bystander CPR is positively associated with increased survival rates after an out-of-hospital cardiac arrest. The study shows significant racial-ethnic disparities in bystander CPR receiving rates at home and in public locations in a national representative sample—this occurred regardless of the racial or ethnic makeup or income level of the neighborhood where the cardiac arrest occurred. The study findings warrant multidimensional, focused public health programs that involve diverse community stakeholders.
The Pick: Shah VA, Thompson RE, Yenokyan G, et al. One-year outcome trajectories and factors associated with functional recovery among survivors of intracerebral and intraventricular hemorrhage with initial severe disability https://jamanetwork.com/journals/jamaneurology/fullarticle/2794291. JAMA Neurol 2022;79(9):856-868.
The Findings: Among 715 survivors of severe intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) with initial poor functional outcomes, 129 participants (18 percent) had died and 308 (43 percent) had achieved modified Rankin score of 0 to 3 by one year. Resolution of ICH and IVH by day 30 were associated with recovery to a good outcome. Hospital events were strongly associated with long-term functional recovery. Further, 30-day recovery models strongly predicted one-year outcomes with significant contributions from the baseline severity factors.
Why It's Important: Therapeutic nihilism associated with severe brain injury is an inappropriately pessimistic view of a patient's outcome and the ability of a patient to benefit from aggressive care. It is critical to understand how the expectation of a poor outcome can become a self-fulfilling prophecy depriving patients of the chance of an outcome that would be acceptable to them. The study showed two of five patients with severe traumatic brain injury have the potential to achieve good functional outcomes within one year and hospital-based care may be a potential target for intervention.
BRENT FOGEL, MD, PHD, FAAN
Professor of Neurology and Human Genetics
David Geffen School of Medicine, UCLA
Los Angeles, CA
The Pick: Ibanez K, Polke J, Hagelstrom RT, et al. Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: A retrospective diagnostic accuracy and prospective clinical validation study https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00462-2/fulltext. Lancet Neurol 2022;21(3):234-245.
The Findings: The authors assessed the ability of whole genome sequencing (WGS) to bioinformatically detect 13 common repeat expansion disorders associated with neurologic disease using a computational tool called ExpansionHunter. They confirmed the accuracy of the detection method using conventional PCR testing.
In a retrospective analysis, Expansion Hunter showed 97.3 percent sensitivity (95 percent CI 94.2 to 99.0) in detecting 221 expansions and 99.6 percent specificity (99.1 to 99.9) in 1,321 normal alleles. In a prospective analysis of nearly 12,000 patients from the 100,000 Genomes Project suspected of having a neurologic disorder, ExpansionHunter identified 81 previously undiagnosed repeat expansions. Of those, PCR confirmed that 84 percent (68) were in the full pathogenic range.
Why It's Important: Repeat expansion disorders are a significant cause of neurologic disease and often can present in a clinically heterogeneous manner. While the majority of genetic testing performed in clinical practice is sequence-based, detection of repeat expansions requires the ordering of disease-specific tests using alternate methodology, such as PCR. Being able to accurately detect repeat expansions using a more common sequencing test, such as WGS—which already can detect sequence changes in both the protein coding and non-coding regions of the genome along with clinically relevant genomic structural change, such as copy number variation—increases the usefulness of such testing for a broad range of neurologic phenotypes. As the cost of clinical WGS continues to drop and it becomes more accessible for routine diagnostic testing, we draw closer to WGS becoming a one-test-fits-all for the vast majority of clinically relevant genetic mutations.
The Picks: Magri S, Nanetti L, Gellera C, et al. Digenic inheritance of STUB1 variants and TBP polyglutamine expansions explains the incomplete penetrance of SCA17 and SCA48 https://www.sciencedirect.com/science/article/pii/S1098360021011175. Genet Med 2022;24(1):29-40.
Barbier M, Davoine CS, Petit E, et al. Intermediate repeat expansions of TBP and STUB1: Genetic modifier or pure digenic inheritance in spinocerebellar ataxias? https://en.x-mol.com/paper/article/1595640179292774400Genet Med 2022; Epub 2022 Nov 23.
The Findings: The genes TBP and STUB1 are associated with dominant genetic spinocerebellar ataxia phenotypes that may resemble Huntington disease, specifically SCA17 and SCA48, respectively. SCA17 is a repeat expansion disorder in which CAG nucleotide repeats greater than 50 in TBP are always associated with disease and intermediate-sized expansions in the range of 41 to 49 repeats show incomplete penetrance. SCA48, in contrast, is caused by mutations that alter or disrupt the STUB1 coding sequence.
In the first publication, 97 percent of 31 affected SCA17 patients with intermediate-sized TBP expansions also carried a heterozygous change in the STUB1 gene, and only individuals with both the TBP intermediate-sized expansion and the STUB1 variant showed disease, suggesting that both genetic changes may be required for disease.
In the second publication, the authors examined a cohort of patients with both SCA17 and SCA48 and noted that 49 percent of 35 patients with SCA17 with intermediate-sized repeats also had a STUB1 variant. They further examined 43 patients with SCA48 and found that 40 percent of them harbored intermediate-sized TBP expansions and that the repeat size correlated with the degree of cognitive impairment and faster disease progression.
Why It's Important: In disorders showing incomplete penetrance or variable phenotypes, it often is difficult to counsel family members on the risk of developing disease. Furthermore, for many genetic conditions, it also often is difficult to provide clear information regarding prognosis early in the course of the disease. These publications establish a model that suggests that while SCA17 is a monogenic dominant disorder for larger expansions, it requires a second genetic insult, most commonly alteration of STUB1, for disease to occur with intermediate-sized expansions. For SCA48, intermediate-sized TBP expansions appear to act as a disease modifier, worsening the severity of the disease. These studies illustrate the interplay that can occur between genes causing neurologic disease and foreshadow how comprehensive genetic information can be better used in the future to counsel patients and family members on the risks of disease development and prognosis.
DIANNA QUAN, MD, FAAN
Professor of Neurology
University of Colorado Denver
The Pick: Cohen JL, Chakraborty P, Fung-Kee-Fung K, et al. In utero enzyme-replacement therapy for infantile-onset Pompe's disease https://www.nejm.org/doi/full/10.1056/NEJMoa2200587. N Engl J Med 2022; 387(23):2150-2158.
The Findings: This paper describes in utero enzyme replacement therapy (ERT) for infantile Pompe's disease due to acid alpha-glucosidase (GAA) deficiency. In its most severe untreated form, patients have multisystem dysfunction affecting cardiac and skeletal muscle; death occurs by age 2. ERT slows the disease, but patients often have irreversible tissue damage by the time therapy begins.
Why It's Important: The study authors describe the use of in utero ERT that may prevent fetal tissue damage and reduce the formation of anti-drug antibodies. This treatment may have significant implications for Pompe's disease as well as a host of other enzyme deficiency disorders.
The Pick: Piehl F, Eriksson-Dufva A, Budzianowska A, et al. Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: The RINOMAX randomized clinical trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2796552. JAMA Neurol 2022;79(11):1105-1112.
The Finding: This paper found benefit from a single infusion of low-dose rituximab at 16 weeks in patients with recent-onset myasthenia gravis. In clinical practice, rituximab is often considered as a later treatment option after other agents, such as azathioprine and mycophenolate, have been tried.
Why It's Important: The JAMA Neurology study suggests that some patients may benefit from earlier treatment. This approach will likely be an avenue of future research and has possible implications for how neurologists should prioritize medications in their myasthenia treatment algorithm.
The Pick: Aggarwal R, Charles-Schoeman C, Schessl J, et al, for the ProDERM trial group. Trial of intravenous immune globulin in dermatomyositis https://www.nejm.org/doi/full/10.1056/NEJMoa2117912. N Engl J Med 2022;387(14):1264-1278.
The Finding: This large, randomized, controlled trial showed that patients with active dermatomyositis improved after 16 weeks of IV immunoglobulin G (IVIG) treatment.
Why It's Important: While many medications, including glucocorticoids and other oral immunosuppressants, are commonly used in dermatomyositis (and other forms of myositis), IVIG is the first therapy approved by the FDA for any of the inflammatory myopathies. This approval may help streamline the prescription of IVIG for select patients with dermatomyositis.
AMY A. PRUITT, MD, FAAN
William N. Kelley Professor of Neurology
Perelman School of Medicine
University of Pennsylvania, Philadelphia, PA
The Pick: Liau LM, Ashkan K, Brem S, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: A phase 3 prospective externally controlled cohort trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2798847. JAMA Oncol 2022: Epub 2022 Nov 17.
The Findings: This international, multicenter, phase 3, prospective, externally controlled, nonrandomized trial compared overall survival in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with a personalized dendritic cell vaccine (DCVax-L) plus standard of care (radiation and temozolomide) against contemporaneous matched external control patients treated with standard of care. It was conducted at 94 sites in four countries. The primary and secondary endpoints compared overall survival in nGBM and rGBM with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Median overall survival (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 months from randomization (22.4 months from surgery) vs. 16.5 months from randomization in control patients. Survival at 48 months from randomization was 15.7 percent vs. 9.9 percent, and at 60 months, it was 13.0 percent vs. 5.7 percent. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 months from relapse vs. 7.8 months among control patients. Survival at 24 and 30 months after recurrence was 20.7 percent vs. 9.6 percent and 11.1 percent vs. 5.1 percent, respectively.
Why It's Important: Glioblastoma remains a highly lethal tumor for which durable therapies are lacking. The trial demonstrated that adding DCVax-L to standard of care resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received standard of care alone. Also noteworthy were the tails of long-term survivors among the treated patients. The study had novel elements: It implemented an innovative design that could help accelerate advances in the field. Its randomized trial design demonstrated the feasibility of using external matched controls. The therapy was based on the idea of provoking a broader immunologic response against the tumor than is available from conventional therapies or from the immune checkpoint inhibitors that have been successful in such metastatic malignancies as non-small cell lung cancer and melanoma, but not in glioblastoma.
Personalized vaccines using autologous rather than standardized antigens address the extreme heterogeneity of glioblastoma and potentially can ensure that the treatment is targeting antigens actually present on the patient's tumor. Also, targeting the full repertoire of antigens by using tumor lysate could prevent the patient's tumor from mutating around the targeted antigens, as has been seen when only one or a few antigens are targeted.
The Pick: Lin NU, Murthy RK, Abramson V, et al., Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: Updated exploratory analysis of the HER2CLIMB randomized clinical trial https://jamanetwork.com/journals/jamaoncology/fullarticle/2799133. JAMA Oncol 2022; Epub 2022 Dec 1.
The Findings: This international multicenter study compared overall survival and intracranial outcomes from tucatinib in combination with trastuzumab and capecitabine alone in patients with ERBB2-positive metastatic breast cancer and brain metastases. At median follow-up of 29.6 months (range, 0.1 to 52.9 months), median overall survival was 9.1 months longer in the tucatinib-combination group (21.6 months; 95 percent CI, 18.1 to 28.5) vs. the placebo-combination group (12.5 months; 95 percent CI, 11.2 to 16.9). Risk of developing new brain lesions at the site of first progression or death was reduced by 45.1 percent in the tucatinib-combination group compared to the placebo-combination group.
Why It's Important: It is estimated that up to 50 percent of patients with ERBB2 (HER2)-positive metastatic brain cancer will develop brain metastases. Previous reports of the HER2CLIMB trial have demonstrated that tucatinib in combination with trastuzumab and capecitabine provides survival and intracranial benefits for patients with ERBB2-positive metastatic breast cancer and brain metastases. This study offered more than 15 months of additional follow-up of such patients.
Tucatinib in combination with trastuzumab and capecitabine improved overall survival while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with ERBB2-positive MBC, including those with brain metastases. It is in the interest of all patients with brain metastases to avoid whole brain radiation therapy, which can have devastating cognitive consequences in the medium and longer term.
The Pick: Farina A, Villagrán-García M, Ciano-Petersen NL, et al. Anti-hu antibodies in patients with neurologic side effects of immune checkpoint inhibitors https://nn.neurology.org/content/10/1/e200058. Neurol Neuroimmunol Neuroinflamm 2022; 10(1):e200058.
The Findings: This study aimed to clinically characterize post-immune checkpoint inhibitor (ICI) Hu antibody (Ab) neurologic disorders in a group of anti- Hu-Ab-positive patients with neurologic, immune-related adverse events (n-irAEs) and compared them with patients with other n-irAEs, ICI-naive patients with Hu-Ab paraneoplastic neurologic syndromes (PNSs) identified in the same study center, and those with Hu-Ab n-irAEs reported elsewhere.
Eleven patients with lung cancers with Hu-Ab and n-irAEs were included (median age, 66 years; range 44 to 76 years; 73percent men). Compared with those with other n-irAEs (n=63), Hu-Ab-positive patients had more frequently co-occurring involvement of both central and peripheral nervous systems (36 percent vs. 8 percent, p=0.02) and limbic (54 percent vs. 14 percent, p<0.01), brainstem (27 percent vs. 5 percent, p=0.02), and dorsal root ganglia (45 percent vs. 5 percent, p<0.01) involvement. The proportion of patients with severe disability (modified Rankin scale score>3) at diagnosis was high. Patients with Hu-Ab had also poorer outcomes and higher mortality. There was no significant difference in terms of clinical features between Hu-Ab n-irAEs and ICI-naive Hu-Ab PNSs (n=92), but there was a poorer outcome (56/78, 71 percent, p 0.01) and higher mortality (26 percent, p<0.01) among the former.
Why It's Important: With the increasing use of ICIs for an expanding group of neoplasms, the spectrum of neurologic complications is evolving, and neurologic consultants should be aware of the hazards of these therapies. The presence of Hu-Ab identifies a subgroup of n-irAEs that consistently reproduce the phenotypes of Hu-Ab-related PNSs, supporting the hypothesis that ICI triggers or unmasks these syndromes. As these patients show high disability and mortality, further studies are required to investigate the underlying immunopathogenic mechanisms and to improve the outcome of HuAb n-irAEs. As numerous other PNSs have been unmasked by ICI use, it will become important to identify patients who should not receive such therapies and to identify those patients with PNS to effect early, potentially stabilizing treatments.
HEALTH POLICY AND TELEMEDICINE
NEIL A. BUSIS, MD, FAAN
Associate Chair, Technology and Innovation
Department of Neurology, NYU Langone Health
Clinical Professor of Medicine, NYU Grossman School of Medicine
New York, NY
The Pick: American Medical Association. Current procedural terminology (CPT) 2023. Chicago, IL: American Medical Association, 2022.
The Findings: This impactful policy, developed in 2022, allows that, effective Jan. 1, 2023, the level of inpatient evaluation and management (E/M) services will be determined by medical decision-making or total time on the day of the encounter. Elements of history and physical examination are no longer mandated for coding and billing purposes. They can be included in clinical notes only as needed for patient care.
Why It's Important: The new rules much more closely reflect the work and time associated with providing patient care by physicians and other qualified health care professionals than the previous rules, which had been in effect since 1997. Streamlining documentation requirements for E/M services may improve patient care and should promote well-being by mitigating administrative burden, one of the biggest drivers of physician and other burnout among qualified health care professionals. This completes the transformation of coding for E/M services that started with outpatient codes in 2021. To take full advantage of the new rules, we will need to reassess what we include in our clinical notes. While current note structures are compatible with the new rules, they may include a lot of extraneous material that imposes undue administrative burdens and impedes communication among providers and between providers and their patients.
The Pick: Mehrotra A, Uscher-Pines L. Informing the debate about telemedicine reimbursement: What do we need to know?https://www.nejm.org/doi/full/10.1056/NEJMp2210790N Engl J Med 2022;387(20):1821-1823.
The Findings: The authors frame the essential questions we need to address if we are to develop optimal telehealth reimbursement policies in the future. They propose that the major areas of uncertainty are whether telemedicine increases spending, improves patient outcomes, and advances health equity.
Why It's Important: Telehealth use markedly increased during the COVID-19 pandemic to protect patients and providers from infection while maintaining access to clinical services. However, the rate of adoption outstripped the rate of evidence of the effectiveness of telehealth. This paper is a distillation of telehealth quality metrics proposed by the National Quality Forum, the American Medical Association, and others.
A unique feature of this paper is that it acknowledges that “telemedicine” means different things in different contexts—that is, that the use of different telemedicine modalities and the frequency with which they are combined with in-person visits can vary between studies. This is a barrier to meta-analyses incorporating different studies since the “dose of telemedicine” may vary between studies. Researchers will need to be more aware of this issue if we are to determine the best use cases and reimbursement and coverage policies for the various telemedicine modalities.
The Pick: Demaerschalk BM, Pines A, Butterfield R, et al, for the Diagnostic accuracy of telemedicine utilized at Mayo Clinic Alix School of Medicine Study Group Investigators. Assessment of clinician diagnostic concordance with video telemedicine in the integrated multispecialty practice at Mayo Clinic during the beginning of COVID-19 pandemic from March to June 2020 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2795871. JAMA Netw Open 2022; 5(9): e2229958.
The Findings: This study aimed to determine the concordance of diagnoses proposed at two-way, real-time, interactive audio-video telemedicine encounters with diagnoses established at in-person visits for patients with new clinical problems. There was a high degree of diagnostic concordance between the two modalities of care, but it varied by the specific clinical circumstances. The diagnostic concordance for neurologic encounters was about 81 percent.
Why It's Important: This study is an important step toward assessing the quality of telehealth encounters. A strength is the study design. Many specialties and clinical conditions were assessed by the researchers using rigorous criteria. A weakness is that only encounters between March 24, 2020, and June 24, 2020, were reviewed. This was well before many clinicians had developed effective remote physical examination techniques and knowledge of the conditions that were best suited for virtual visits. Given what we've learned over the past few years, the concordance of telehealth and in-person diagnoses for certain neurologic patients might be considerably greater now than what was found in this study.
JENNIFER BICKEL, MD, FAAN
Chief Wellness Officer
Senior Member, Department of Neuro-oncology
Professor of Oncologic Sciences
University of South Florida Morsani School of Medicine
The Picks: Addressing health worker burnout: The US Surgeon General's advisory on building a thriving workforce 2022. National Academy of Medicine 2002. National plan for health workforce wellbeing https://nam.edu/initiatives/clinician-resilience-and-well-being/national-plan-for-health-workforce-well-being/. Washington, DC: The National Academies Press.
Shanafelt TD, West CP, Dyrbye LN, et al. Changes in burnout and satisfaction with work-life integration in physicians over the first 2 years of the COVID-19 pandemic https://www.mayoclinicproceedings.org/article/S0025-6196(22)00515-8/fulltext. Mayo Clin Proc 2022;97(12):2248-2258.
The Joint Commission announces major standards reduction and freezes hospital accreditation fees to provide relief to healthcare organizations. https://bit.ly/3hKDcGp. Accessed Dec 21, 2022.
The Findings: In 2022, we saw major initiatives from national leaders to address burnout among health care workers. The US Surgeon General's office published an advisory to inform the public that the well-being of health care workers is directly related to the well-being of our communities. The National Academy of Medicine released a national plan for health workforce well-being. And in Mayo Clinic Proceedings, Shanafelt and colleagues underscored the barriers to well-being and wellness. Finally, in a major step toward reducing administrative burden, the Joint Commission eliminated 14 percent of its standards across its accreditation programs in an effort to reduce unnecessary and redundant requirements.
Why It's Important: As burnout rates increase among physicians nationwide, the barriers to well-being and wellness can seem insurmountable. However, despite these challenges, the movement to improve wellness in health care made tremendous progress this year. Burnout is an existential threat to the health of our communities, and leaders across the country are taking notice.
In 2022, an understanding of the complex causes and solutions to burnout has evolved to look beyond personal resilience and the electronic health record. Indeed, those of us who focus on wellness—and these publications—recognize that culture, meaning in work, inclusion, leadership, and a sense of feeling valued are all necessary elements for a thriving and healthy workforce.
This gives me hope and strengthens the vision I have for a thriving workforce in neurology and beyond. The AAN supports that messaging and has called on legislators, payers, health technology venues, accrediting bodies, and others to act upon this urgent crisis in health care. As chair of the AAN Wellness Subcommittee, I can attest that 2022 has included ongoing executive support from the AAN with expanded collaborations across the academy's committees, including education, practice management, advocacy, academic neurology, and more. These top-level reports and initiatives give me hope and strengthen the vision I have for a thriving workforce in neurology and beyond.
ANDREW SPECTOR, MD, FAASM
Associate Professor of Neurology
The Pick: Senate Bill S https://www.congress.gov/bill/117th-congress/senate-bill/623. 623
The Findings: The bill, the Sunshine Protection Act, passed on March 15, 2022. The bill would eliminate the biannual clock changes and fix the United States on daylight saving time. The passage of this bill in the Senate mobilized the sleep community in opposition and garnered a huge amount of attention this year.
Why It's Important: While there is consensus that clock changes are harmful, there is widespread medical agreement that permanent daylight saving time would come with substantial negative health consequences compared with the biologically aligned standard time. In 2022, the AAN Sleep Section and health care organizations—including the American Academy of Sleep Medicine and the American Medical Association—mobilized to successfully oppose this bill.
The Pick: Kaufmann CN, Spira AP, Wickwire EM, et al. Declining trend in use of medications for sleep disturbance in the United States from 2013 to 2018 https://jcsm.aasm.org/doi/10.5664/jcsm.10132. J Clin Sleep Med 2022;18(10):2459-2465.
The Findings: The study showed that the use of sedative-hypnotic medications declined by 31 percent from 2013 to 2018, driven largely by an 86 percent decline in usage among those over 80 years of age.
Why It's Important: Sleep experts agree that sedative-hypnotic medications are suboptimal treatments for chronic insomnia and come with substantial risks, particularly for older patients who are at higher risk for cognitive impairment and falls when using these drugs. It is encouraging that use of these drugs declined greatly among those older than 80 years old. How this trend was impacted by the pandemic and its associated sleep disruption remains to be seen.