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Merino, Jose G. MD, MPhil; Ciccarelli, Olga MD, PhD, FRCP; Worrall, Bradford B. MD, MSc; Amato, Anthony A. MD; Burch, Rebecca MD; Corboy, John R. MD; Dalmau, Josep O. MD, PhD; Graff-Radford, Jonathan MD; Graves, Jennifer MD, PhD, MAS; Hedera, Peter MD, PhD; Hershey, Linda A. MD, PhD; Jobst, Barbara C. MD, PhD; Pulst, Stefan M. MD; Shellhaas, Renee A. MD, MS; Strowd, Roy E. III MD
doi : 10.1212/WNL.0000000000011204
pg. 1-9
F2R Polymorphisms and Clopidogrel Efficacy and Safety: Another Step Toward Precision Medicine.
Cole, John W. MD, MS
doi : 10.1212/WNL.0000000000011085
pg. 10-11
Has the Time Come to Revisit Our Standard Measures of Disability Progression in Multiple Sclerosis?.
Kalincik, Tomas MD, PhD; Sormani, Maria Pia PhD; Tur, Carmen MD, PhD
doi : 10.1212/WNL.0000000000011120
pg. 12-13
Ken Swaiman, MD (1931-2020).
Ashwal, Stephen; Rosman, N. Paul
doi : 10.1212/WNL.0000000000011200
pg. 14
F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients With Minor Stroke or TIA.
Pan, Yuesong PhD *; Wangqin, Runqi MD, MHS *; Li, Hao PhD; Wang, Yilong MD, PhD; Meng, Xia MD, PhD; Johnston, S. Claiborne MD, PhD; Simon, Tabassome MD, PhD; Lin, Jinxi MD, PhD; Zhao, Xingquan MD, PhD; Liu, Liping MD, PhD; Wang, David DO; Wang, Yongjun MD
doi : 10.1212/WNL.0000000000011078
pg. e1-e9
AB Objective: To investigate the association between protease-activated receptor-1 (PAR-1) gene F2R polymorphisms and efficacy of clopidogrel for minor stroke or TIA. Methods: Three single nucleotide polymorphisms (CYP2C19*2 [681G>A, rs4244285], CYP2C19*3 [636G>A, rs4986893], and F2R [IVSn-14 A/T, rs168753]) were genotyped among 2,924 patients randomized to clopidogrel plus aspirin (n = 1,461) or aspirin alone (n = 1,463). The primary efficacy outcome was new stroke (ischemic or hemorrhagic) and the safety outcome was any bleeding. Results: Overall, 859 (29.4%) were AA homozygotes, 1,479 (50.6%) were AT heterozygotes, and 586 (20.0%) were TT homozygotes for F2R IVSn-14 polymorphisms; 1,716 (58.7%) were carriers of at least 1 CYP2C19 loss-of-function allele (*2 or *3). Compared with aspirin alone, patients with clopidogrel-aspirin treatment had a low risk of new stroke in patients with AT genotype (7.6% vs 11.3%; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89) and TT genotype (5.8% vs 11.6%; HR, 0.46; 95% CI, 0.25-0.82) but not in carriers of the AA genotype (10.8% vs 11.6%; HR, 0.95; 95% CI, 0.63-1.44) (p = 0.03 for interaction). The association between F2R IVSn-14 A/T polymorphism and clopidogrel response was present regardless of the carrier status of the CYP2C19 loss-of-function alleles. The F2R IVSn-14 genotypes were not associated with the risk of any bleeding for clopidogrel-aspirin treatment (p = 0.66 for interaction). Conclusions: Among patients with minor ischemic stroke or TIA who were receiving clopidogrel and aspirin, those carrying the F2R IVSn-14 T allele had a lower rate of recurrent stroke than those who were not. Clinicaltrials.gov Identifier: NCT00979589. (C) 2021 American Academy of Neurology
Use of the ABC/2 Method to Select Patients for Thrombectomy After 6 Hours of Symptom Onset.
Boisseau, William MD; Dargazanli, Cyril MD; Smajda, Stanislas MD; Capron, Jean MD; Piotin, Michel MD, PhD; Ducroux, Celina MD, MSc; Shamy, Michel MD; Dowlatshahi, Dariush MD, PhD; Aviv, Richard I. MD; Fahed, Robert MD
doi : 10.1212/WNL.0000000000010999
pg. e10-e18
AB Objective: To determine whether the ABC/2 method could accurately and reliably measure infarct volume and guide thrombectomy decision in acute stroke cases presenting with late or unknown onset. Methods: Four physicians who routinely use MRI for acute stroke imaging, blinded to the RAPID results, measured the diffusion-weighted imaging (DWI) infarct volume using the ABC/2 method. Measurements with ABC/2 (the index test) were compared with RAPID (the reference standard) to calculate sensitivity, specificity, and accuracy measures for various volume cutpoints. Thrombectomy decisions based on RAPID and raters' measurements using the criteria from the Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late-Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial criteria were compared. Interrater and intrarater agreement was measured using kappa statistics. Results: Accuracy with the ABC/2 method was greater than 80% for each rater and each volume cut point. Interrater and intrarater agreement was substantial to excellent for each volume cut point. Treatment decisions with ABC/2 volume estimations showed strong interrater and intrarater agreement, and led to similar thrombectomy decisions compared with RAPID in more than 85% of cases. Conclusion: DWI infarct volume measurement using ABC/2 method shows strong accuracy and reliability and may be an acceptable alternative to RAPID software for the application of DAWN criteria for thrombectomy decision-making. (C) 2021 American Academy of Neurology
Safety of Aspirin Use in Patients With Stroke and Small Unruptured Aneurysms.
Weng, Jian-Cong MD; Wang, Jie MD; Du, Xin MD; Li, Hao MD; Jiao, Yu-Ming MD; Fu, Wei-Lun MD; Huo, Ran MD; Yan, Zi-Han MD; Xu, Hong-Yuan MD; Wang, Shuo MD; Cao, Yong MD; Zhao, Ji-Zong MD; on behalf of the Small Unruptured Aneurysms Study Group
doi : 10.1212/WNL.0000000000010997
pg. e19-e29
AB Objective: We initiated a multicenter, prospective cohort study to test the hypothesis that aspirin is safe for patients with ischemic cerebrovascular disease (ICVD) harboring unruptured intracranial aneurysms (UIAs) <7 mm. Methods: This prospective, multicenter cohort study consecutively enrolled 1,866 eligible patients with ICVD harboring UIAs <7 mm in diameter from 4 hospitals between January 2016 and August 2019. Baseline and follow-up patient information, including the use of aspirin, was recorded. The primary endpoint was aneurysm rupture. Results: After a total of 4,411.4 person-years, 643 (37.2%) patients continuously received aspirin treatment. Of all included patients, rupture occurred in 12 (0.7%). The incidence rate for rupture (IRR) was 0.27 (95% confidence interval [CI] 0.15-0.48) per 100 person-years. The IRRs were 0.39 (95% CI 0.21-0.72) and 0.06 (95% CI 0.010-0.45) per 100 person-years for the nonaspirin and aspirin groups, respectively. In the multivariate analysis, uncontrolled hypertension and UIAs 5 to <7 mm were associated with a high rate of aneurysm rupture, whereas aspirin use was associated with a low rate of aneurysm rupture. Compared with other groups, the high-risk group (UIAs 5 to <7 mm with concurrent uncontrolled hypertension) without aspirin had higher IRRs. Conclusion: Aspirin is a safe treatment for patients with concurrent small UIAs and ICVD. Patients who are not taking aspirin in the high-risk group warrant intensive surveillance. ClinicalTrials.gov Identifier: NCT02846259. Classification of Evidence: This study provides Class III evidence that for patients harboring UIAs <7 mm with ICVD, aspirin does not increase the risk of aneurysm rupture. (C) 2021 American Academy of Neurology
Patterns of Use and Discontinuation of Secondary Prevention Medications After Stroke.
Dalli, Lachlan L. BBiomedSc (Hons); Kim, Joosup PhD; Thrift, Amanda G. PhD; Andrew, Nadine E. PhD; Sanfilippo, Frank M. PhD; Lopez, Derrick PhD; Grimley, Rohan MBBS; Lannin, Natasha A. PhD; Wong, Lillian MBBS; Lindley, Richard I. MD; Campbell, Bruce C.V. PhD; Anderson, Craig S. PhD; Cadilhac, Dominique A. PhD; Kilkenny, Monique F. PhD; on behalf of the AuSCR Consortium
doi : 10.1212/WNL.0000000000011083
pg. e30-e41
AB Objective: To investigate whether certain patient, acute care, or primary care factors are associated with medication initiation and discontinuation in the community after stroke or TIA. Methods: This is a retrospective cohort study using prospective data on adult patients with first-ever acute stroke/TIA from the Australian Stroke Clinical Registry (April 2010 to June 2014), linked with nationwide medication dispensing and Medicare claims data. Medication users were those with >=1 dispensing in the year postdischarge. Discontinuation was assessed among medication users and defined as having no medication supply for >=90 days in the year postdischarge. Multivariable competing risks regression, accounting for death during the observation period, was conducted to investigate factors associated with time to medication discontinuation. Results: Among 17,980 registry patients with stroke/TIA, 91.4% were linked to administrative datasets. Of these, 9,817 adults with first-ever stroke/TIA were included (45.4% female, 47.6% aged >=75 years, and 11.4% intracerebral hemorrhage). While most patients received secondary prevention medications (79.3% antihypertensive, 81.8% antithrombotic, and 82.7% lipid-lowering medication), between one-fifth and one-third discontinued treatment over the subsequent year postdischarge (20.9% antihypertensive, 34.1% antithrombotic, and 28.5% lipid-lowering medications). Prescription at hospital discharge (sub-hazard ratio [SHR] 0.70; 95% confidence interval [CI] 0.62-0.79), quarterly contact with a primary care physician (SHR 0.62; 95% CI 0.57-0.67), and prescription by a specialist physician (SHR 0.87; 95% CI 0.77-0.98) were all inversely associated with antihypertensive discontinuation. Conclusions: Patterns of use of secondary prevention medications after stroke/TIA are not optimal, with many survivors discontinuing treatment within 1 year postdischarge. Improving postdischarge care for patients with stroke/TIA is needed to minimize unwarranted discontinuation. (C) 2021 American Academy of Neurology
New Index for Multiple Chronic Conditions Predicts Functional Outcome in Ischemic Stroke.
Jiang, Xiaqing MD; Wang, Lu PhD; Morgenstern, Lewis B. MD; Cigolle, Christine T. MD; Claflin, Edward S. MD; Lisabeth, Lynda D. PhD
doi : 10.1212/WNL.0000000000010992
pg. e42-e53
AB Objective: To determine whether a new index for multiple chronic conditions (MCCs) predicts poststroke functional outcome (FO), we developed and internally validated the new MCC index in patients with ischemic stroke. Methods: A prospective cohort of patients with ischemic stroke (2008-2017) was interviewed at baseline and 90 days in the Brain Attack Surveillance in Corpus Christi Project. An average of 22 activities of daily living (ADL)/instrumental ADL (IADL) items measured the FO score (range 1-4) at 90 days. A FO score >3 (representing a lot of difficulty with ADL/IADLs) was considered unfavorable FO. A new index was developed using machine learning techniques to select and weight conditions and prestroke impairments. Results: Prestroke modified Rankin Scale (mRS) score, age, congestive heart failure (CHF), weight loss, diabetes, other neurologic disorders, and synergistic effects (dementia x age, CHF x renal failure, and prestroke mRS x prior stroke/TIA) were identified as important predictors in the MCC index. In the validation dataset, the index alone explained 31% of the variability in the FO score, was well-calibrated (p = 0.41), predicted unfavorable FO well (area under the receiver operating characteristic curve 0.81), and outperformed the modified Charlson Comorbidity Index in predicting the FO score and poststroke mRS. Conclusions: A new MCC index was developed and internally validated to improve the prediction of poststroke FO. Novel predictors and synergistic interactions were identified. Classification of Evidence: This study provides Class II evidence that in patients with ischemic stroke, an index for MCC predicts FO at 90 days. (C) 2021 American Academy of Neurology
Five-Year Prognosis After TIA or Minor Ischemic Stroke in Asian and Non-Asian Populations.
Hoshino, Takao MD; Uchiyama, Shinichiro MD; Wong, Lawrence K.S. MD; Kitagawa, Kazuo MD; Charles, Hugo BST; Labreuche, Julien BST; Lavallee, Philippa C. MD; Albers, Gregory W. MD; Caplan, Louis R. MD; Donnan, Geoffrey A. MD; Ferro, Jose M. MD; Hennerici, Michael G. MD; Molina, Carlos MD; Rothwell, Peter M. MD; Steg, P. Gabriel MD; Touboul, Pierre-Jean MD; Vicaut, Eric MD; Amarenco, Pierre MD; on behalf of the TIA registry.org Investigators
doi : 10.1212/WNL.0000000000010995
pg. e54-e66
AB Objective: To determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asian patients with those of non-Asian patients, in the context of modern guideline-based prevention strategies. Methods: This is a subanalysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. Results: No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88-1.37; p = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90-1.51; p = 0.24) between Asian and non-Asian patients. Asian participants were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09-4.57; p = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11-3.29; p = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02-1.90; p = 0.037) patients. Conclusion: The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asian participants had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups. Classification of Evidence: This study provides Class I evidence that among people who experienced TIA or minor stroke, Asian patients have a similar 5-year risk of cardiovascular death, stroke, and acute coronary syndrome as non-Asian patients. (C) 2021 American Academy of Neurology
Association of Angiotensin II-Stimulating Antihypertensive Use and Dementia Risk: Post Hoc Analysis of the PreDIVA Trial.
van Dalen, Jan Willem PhD *; Marcum, Zachary A. PharmD, PhD *; Gray, Shelly L. PharmD, MS; Barthold, Douglas PhD; Moll van Charante, Eric P. MD, PhD; van Gool, Willem A. MD, PhD; Crane, Paul K. MD, MPH; Larson, Eric B. MD, MPH; Richard, Edo MD, PhD
doi : 10.1212/WNL.0000000000010996
pg. e67-e80
AB Objective: To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, [beta]-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis." Methods: We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 +/- 2.5) years. Results: After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease. Conclusions: Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment. (C) 2021 American Academy of Neurology
Topographic Distribution of Amyloid-[beta], Tau, and Atrophy in Patients With Behavioral/Dysexecutive Alzheimer Disease.
Therriault, Joseph BSc; Pascoal, Tharick A. MD, PhD; Savard, Melissa MSc; Benedet, Andrea L. PhD; Chamoun, Mira PhD; Tissot, Cecile BSc; Lussier, Firoza BSc; Kang, Min Su BSc; Thomas, Emilie PhD; Terada, Tatsuhiro MD, PhD; Rej, Soham MD, MSc; Massarweh, Gassan PhD; Nasreddine, Ziad MD, FRCPC; Vitali, Paolo MD, PhD; Soucy, Jean-Paul MD, MSc; Saha-Chaudhuri, Paramita PhD; Gauthier, Serge MD, FRCPC; Rosa-Neto, Pedro MD, PhD
doi : 10.1212/WNL.0000000000011081
pg. e81-e92
AB Objective: To determine the associations between amyloid-PET, tau-PET, and atrophy with the behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, and how they correlate to clinical symptoms. Methods: We assessed 15 patients with behavioral/dysexecutive AD recruited from a tertiary care memory clinic, all of whom had biologically defined AD. They were compared with 25 patients with disease severity- and age-matched amnestic AD and a group of 131 cognitively unimpaired (CU) elderly individuals. All participants were evaluated with amyloid-PET with [18F]AZD4694, tau-PET with [18F]MK6240, MRI, and neuropsychological testing. Results: Voxelwise contrasts identified patterns of frontal cortical tau aggregation in behavioral/dysexecutive AD, with peaks in medial prefrontal, anterior cingulate, and frontal insular cortices in contrast to amnestic AD. No differences were observed in the distribution of amyloid-PET or atrophy as determined by voxel-based morphometry. Voxelwise area under the receiver operating characteristic curve analyses revealed that tau-PET uptake in the medial prefrontal, anterior cingulate, and frontal insular cortices were best able to differentiate between behavioral/dysexecutive and amnestic AD (area under the curve 0.87). Voxelwise regressions demonstrated relationships between frontal cortical tau load and degree of executive dysfunction. Conclusions: Our results provide evidence of frontal cortical involvement of tau pathology in behavioral/dysexecutive AD and highlight the need for consensus clinical criteria in this syndrome. (C) 2021 American Academy of Neurology
Predictors of Mortality in Older Adults With Epilepsy: Implications for Learning Health Systems.
Blank, Leah J. MD, MPH; Acton, Emily K. BS; Willis, Allison W. MD, MS
doi : 10.1212/WNL.0000000000011079
pg. e93-e101
AB Objective: To determine the incidence of epilepsy and subsequent 5-year mortality among older adults, as well as characteristics associated with mortality. Methods: This was a retrospective cohort study of Medicare beneficiaries age 65 or above with at least 2 years enrollment before January 2009. Incident epilepsy cases were identified in 2009 using ICD-9-CM code-based algorithms; death was assessed through 2014. Cox regression models examined the association between 5-year mortality and incident epilepsy, and whether mortality differed by sociodemographic characteristics or comorbid disorders. Results: Among the 99,990 of 33,615,037 beneficiaries who developed epilepsy, most were White (79.7%), female (57.3%), urban (80.5%), and without Medicaid (71.3%). The 5-year mortality rate for incident epilepsy was 62.8% (62,838 deaths). In multivariable models, lower mortality was associated with female sex (adjusted hazards ratio [AHR] 0.85, 95% confidence interval [CI] 0.84-0.87), Asian race (AHR 0.82, 95% CI 0.76-0.88), and Hispanic ethnicity (AHR 0.81, 95% CI 0.76-0.84). Hazard of death increased with comorbid disease burden (per 1-point increase: AHR 1.27, 95% CI 1.26-1.27) and Medicaid coinsurance (AHR 1.17, 95% CI 1.14-1.19). Incident epilepsy was particularly associated with higher mortality when diagnosed after another neurologic condition: Parkinson disease (AHR 1.29, 95% CI 1.21-1.38), multiple sclerosis (AHR 2.13, 95% CI 1.79-2.59), dementia (AHR 1.33, 95% CI 1.31-1.36), traumatic brain injury (AHR 1.55, 95% CI 1.45-1.66), and stroke/TIA (AHR 1.20, 95% CI 1.18-1.21). Conclusions: Newly diagnosed epilepsy is associated with high 5-year mortality among Medicare beneficiaries. Future studies that parse the interplay of effects from underlying disease, race, sex, and poverty on mortality will be critical in the design of learning health care systems to reduce premature deaths. (C) 2021 American Academy of Neurology
Accuracy of Calculated Free Valproate Levels in Adult Patients With Status Epilepticus.
Fisch, Urs MD, PhD; Baumann, Sira M.; Semmlack, Saskia MD; Marsch, Stephan MD, PhD; Ruegg, Stephan MD; Sutter, Raoul MD
doi : 10.1212/WNL.0000000000011000
pg. e102-e110
AB Objective: To test the accuracy of an equation in adult patients with status epilepticus that calculates the free concentration of serum valproic acid (fVPA) from the total concentration of serum valproic acid (tVPA) and serum albumin. Methods: All adult patients with status epilepticus who were treated at a Swiss academic medical center between 2005 and 2018 with concurrent measurements of tVPA, fVPA, and serum albumin were included. fVPA was categorized as subtherapeutic, therapeutic (5-10 mg/L), or supratherapeutic. Agreement was defined as the proportion of measured and calculated fVPA falling within the same category. Results: Of 676 patients with status epilepticus, 104 had 506 measurements, with a median of 3 (interquartile range [IQR] 1.5-6.5) per patient. The median tVPA was 43.5 mg/L (27.4-63.6), with measured fVPA 9.1 mg/L (4.5-14.7) and calculated fVPA 10.1 mg/L (7.0-13.0), respectively. The median deviation of calculated from measured fVPA was -0.8 mg/L (-3.2 to 2.5) with 336 measurements >1 mg/L. While the association between measured and calculated fVPA was linear (regression coefficient 1.1, 95% confidence interval 0.9-1.2, p < 0.0001), the agreement on effective drug levels did not match in 39.8% of measurements regardless of serum albumin levels, with calculated fVPA overestimating measured fVPA in 30.4%. tVPA and serum albumin independently influenced the accuracy of the calculated fVPA in the multivariable model. Conclusions: Calculated fVPA is inaccurate when using the proposed equation in adult patients with status epilepticus, calling for drug monitoring based on measured fVPA in this context. (C) 2021 American Academy of Neurology
Reliability of Outcome Measures in Clinical Trials in Secondary Progressive Multiple Sclerosis.
Koch, Marcus W. MD, PhD; Mostert, Jop MD, PhD; Repovic, Pavle MD, PhD; Bowen, James D. MD; Uitdehaag, Bernard MD, PhD; Cutter, Gary PhD
doi : 10.1212/WNL.0000000000011123
pg. e111-e120
AB Objective: To investigate the reliability of clinical outcomes in secondary progressive multiple sclerosis (SPMS) trials, we compared the frequency of progression and improvement events on different clinical outcome measures in the placebo arms of 2 large randomized controlled trial (RCT) datasets. Methods: Using original trial data from the placebo arms of IMPACT (International MS Secondary Progressive Avonex Controlled Trial) and ASCEND (A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis), 2 large RCTs in SPMS, we compared disability progression and similarly defined improvement with and without 3- or 6-month confirmation on the outcome measures Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and their combinations. Results: In both datasets, the EDSS showed the highest rates of improvement over time, and the smallest difference between progression and improvement rates, followed by the T25FW and the 9HPT. For the T25FW and 9HPT, improvement rates were fairly stable over time and remained at below or around the 10% level. For the EDSS, improvement rates increased in parallel with disability progression rates. Conclusions: All investigated outcome measures in SPMS showed some evidence of random variation and measurement error, the T25FW and 9HPT less so than the more established outcome EDSS. Our findings are relevant for the design and critical appraisal of trials in SPMS. (C) 2021 American Academy of Neurology
Video-Polysomnographic Assessment for the Diagnosis of Disorders of Arousal in Children.
Lopez, Regis MD, PhD; Laganiere, Christine MA; Chenini, Sofiene MD; Rassu, Anna Laura MD; Evangelista, Elisa MD; Barateau, Lucie MD, PhD; Jaussent, Isabelle PhD; Dauvilliers, Yves MD, PhD
doi : 10.1212/WNL.0000000000011091
pg. e121-e130
AB Objectives: To highlight the slow-wave sleep (SWS) fragmentation and validate the video-polysomnographic (vPSG) criteria and cutoffs for the diagnosis of disorders of arousal (DOA) in children, as already reported in adults. Methods: One hundred children (66 boys, 11.0 +/- 3.3 years) with frequent episodes of DOA and 50 nonparasomniac children (32 boys, 10.9 +/- 3.9 years) underwent vPSG recording to quantify SWS characteristics (number of N3 sleep interruptions, fragmentation index, slow/mixed and fast arousal ratios, and indexes per hour) and associated behaviors. We compared SWS characteristics in the 2 groups and defined the optimal cutoff values for the diagnosis of DOA using receiver operating characteristic curves. Results: Patients with DOA had higher amounts of N3 and REM sleep, number of N3 interruptions, SWS fragmentation, and slow/mixed arousal indexes than controls. The highest area under the curve (AUC) values were obtained for SWS fragmentation and slow/mixed arousal indexes with satisfactory classification performances (AUC 0.80, 95% confidence interval [CI] 0.73-0.87; AUC 0.82, 95% CI 0.75-0.89). SWS fragmentation index cutoff value of 4.1/h reached a sensitivity of 65.0% and a specificity of 84.0%. Slow/mixed arousal index cutoff of 3.8/h reached a sensitivity of 69.0% and a specificity of 82.0%. At least one parasomniac episode was recorded in 63.0% of patients and none of the controls. Combining behavioral component by vPSG increased sensitivity of both biomarkers to 83% and 89%, respectively. Conclusions: We confirmed that SWS fragmentation and slow/mixed arousal indexes are 2 relevant biomarkers for the diagnosis of DOA in children, with different cutoffs obtained than those validated in adults. Classification of Evidence: This study provides Class III evidence that SWS fragmentation and slow/mixed arousal indexes on vPSG accurately identify children with DOA. (C) 2021 American Academy of Neurology
Longitudinal Changes in the Retinal Microstructures of Eyes With Chiasmal Compression.
Lee, Ga-In MD *; Son, Ki Young MD *; Park, Kyung-Ah MD, PhD; Kong, Doo-Sik MD, PhD; Oh, Sei Yeul MD, PhD
doi : 10.1212/WNL.0000000000011087
pg. e131-e140
AB Objective: To test the hypothesis that there was a temporal change in the retinal microstructure after decompression surgery for chiasmal compression, the 1-year longitudinal changes in the inner and outer retinal thickness after decompression surgery were analyzed using spectral-domain optical coherence tomography (SD-OCT) with linear mixed-effects models. Methods: SD-OCT was obtained from 87 eyes with chiasmal compression and compared to 100 healthy controls. The preoperative and 1-year postoperative longitudinal changes in the retinal layer thickness were measured. The thickness of each of the following retinal layers was analyzed: the macular retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), the inner nuclear layer, the outer plexiform layer, the outer nuclear layer, and the photoreceptor layer. Results: The RNFL, GCL, and IPL showed thinning at a rate of 1.068 [mu]m/y (95% confidence interval [CI], 0.523, 1.613), 1.189 [mu]m/y (95% CI 0.452, 1.925), and 1.177 [mu]m/y (95% CI 0.645, 1.709), respectively, after decompression surgery. The preoperative thickness of the intraretinal layer was associated with postoperative visual field recovery (RNFL, odds ratio [OR] 1.221, 95% CI 1.058, 1.410; GCL, OR 1.133, 95% CI 1.024, 1.254; and IPL, OR 1.174, 95% CI 1.002, 1.376). Conclusions: The changes in retinal microstructure persisted and progressed in eyes with chiasmal compression after decompression surgery. The findings provide insight into the biological and anatomical sequelae following chiasmal compression. The preoperative thickness of the inner retinal layers was associated with postoperative visual field recovery. (C) 2021 American Academy of Neurology
Differential Neuropsychological Profile of Patients With Amyotrophic Lateral Sclerosis With and Without C9orf72 Mutation.
Iazzolino, Barbara PsyD; Peotta, Laura PsyD; Zucchetti, Jean Pierre MD, MS; Canosa, Antonio MD, PhD; Manera, Umberto MD; Vasta, Rosario MD; Grassano, Maurizio MD; Palumbo, Francesca MD; Brunetti, Maura BSc; Barberis, Marco BSc; Sbaiz, Luca BSc; Moglia, Cristina MD, PhD; Calvo, Andrea MD, PhD, FAAN; Chio, Adriano MD, FAAN
doi : 10.1212/WNL.0000000000011093
pg. e141-e152
AB Objective: To determine whether the neuropsychological profiles of patients with amyotrophic lateral sclerosis (ALS) with (ALSC9+) and without (ALSC9-) C9orf72 expansion are different, we administered a battery of neuropsychological tests to 741 patients with ALS (68 ALSC9+ and 673 ALSC9-) and 129 controls. Methods: The study population includes 741 patients with ALS who were consecutively diagnosed at the Turin ALS expert center in the 2010-2018 period and who underwent both cognitive/behavioral and genetic testing. Patients' neuropsychological patterns were compared (1) at the same degree of cognitive and behavioral deficit according to the revised ALS-Frontotemporal Dementia Consensus Criteria and (2) at the same level of motor impairment according to the King staging system. Results: Despite being about 7 years younger, ALSC9+ patients had significantly lower scores in tests exploring executive function and verbal memory both when classified as cognitively normal and when diagnosed in the intermediate cognitive categories. Considering the clinical perspective, ALSC9+ patients showed significantly lower scores compared to ALSC9- patients at King stage 1 and 3 in almost all the examined neuropsychological domains; at King stage 2, ALSC9+ patients were more severely affected only in the verbal memory domain. Behavioral function was comparably impaired in the 2 cohorts. Conclusions: ALSC9+ patients show a different neuropsychological profile compared to ALSC9- patients, being more impaired in executive functions and verbal memory domains at all King stages. Verbal memory emerged as a particularly vulnerable function in ALSC9+, with worse performances even when patients were still classified as cognitively normal. (C) 2021 American Academy of Neurology
Optic Nerve Cavernous Venous Malformation.
Anglaret, Sophie MD; Lecler, Augustin MD, PhD
doi : 10.1212/WNL.0000000000011092
pg. 31-32
Opsoclonus Myoclonus Ataxia Syndrome in the Setting of COVID-19 Infection.
Shah, Priyank Bharatkumar MD, DM; Desai, Soaham Dilip MD, DM
doi : 10.1212/WNL.0000000000010978
pg. 33
Opinion and Special Articles: Remote Evaluation of Acute Vertigo: Strategies and Technological Considerations.
Green, Kemar E. DO; Pogson, Jacob M. MClinAud, PhD; Otero-Millan, Jorge PhD; Gold, Daniel R. DO; Tevzadze, Nana MD, PhD; Saber Tehrani, Ali S. MD; Zee, David S. MD; Newman-Toker, David E. MD, PhD; Kheradmand, Amir MD
doi : 10.1212/WNL.0000000000010980
pg. 34-38
AB Patients with acute vestibular disorders are often a diagnostic challenge for neurologists, especially when the evaluation must be conducted remotely. The clinical dilemma remains: Does the patient have a benign peripheral inner ear problem or a worrisome central vestibular disorder, such as a stroke? The use of a focused history and the virtual HINTS (head impulse test, nystagmus evaluation, and test of skew) examination are key steps towards correctly diagnosing and triaging the acute vertiginous patient. When looking for signs of vestibulo-ocular dysfunction, there are important technological and practical considerations for an effective clinical interpretation. (C) 2021 American Academy of Neurology
Pearls & Oy-sters: Calcified Cerebral Embolus: A Smoking Gun Guiding Acute Stroke Therapy and Secondary Prevention.
Bres Bullrich, Maria MD; Pandey, Sachin MD; Mayich, Michael MD; McConvey, Kayla MD; Fridman, Sebastian MD, MPH; Mai, Lauren M. MD; Sposato, Luciano A. MD, MBA
doi : 10.1212/WNL.0000000000010805
pg. e153-e156
Teaching NeuroImages: When the Teeth are the Clue to the Etiology of an Epileptic Encephalopathy.
Leao, Victor Hugo Pantoja MD; Aragao, Marcelo de Melo MD, MSc; Pinho, Ricardo Silva MD, PhD; Masruha, Marcelo Rodrigues MD, PhD
doi : 10.1212/WNL.0000000000010758
pg. e157-e158
Teaching NeuroImages: Intraspinal Gouty Tophus.
Si, Meng MD; Cong, Menglin MD; Wang, Dandan BD; Ma, Hecheng MD
doi : 10.1212/WNL.0000000000010761
pg. e159-e160
Editors' Note: Simple MRI Score Aids Prediction of Dementia in Cerebral Small Vessel Disease.
Ganesh, Aravind MD, DPhil; Galetta, Steven MD
doi : 10.1212/WNL.0000000000011202
pg. 39
Reader Response: Simple MRI Score Aids Prediction of Dementia in Cerebral Small Vessel Disease.
Nation, Daniel A.; Kapoor, Arunima
doi : 10.1212/WNL.0000000000011203
pg. 39-40
Reader Response: Simple MRI Score Aids Prediction of Dementia in Cerebral Small Vessel Disease.
Yuan, Junliang
doi : 10.1212/WNL.0000000000011205
pg. 40
