Title | Literature Commentary |
OCR Text | Show Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD Literature Commentary In this issue of the Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD, and Mark L. Moster, MD, discuss the following 6 articles: 1. Mac Grory B, Schrag M, Biousse V, Furie KL, Gerhard-Herman M, Lavin PJ, Sobrin L, Tjoumakaris SI, Weyand CM, Yaghi S; American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Council on Peripheral Vascular Disease. Management of central retinal artery occlusion: a scientific statement from the American Heart Association. Stroke. 2021;52:e282–e294. 2. Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020;588:124–129. 3. Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B; MYACOR Study Group. Comparison of corticosteroid tapering regimens in myasthenia gravis: a randomized clinical trial. JAMA Neurol. 2021;78:426–433. 4. Mollan SP, Mitchell JL, Ottridge RS, Aguiar M, Yiangou A, Alimajstorovic Z, Cartwright DM, Grech O, Lavery GG, Westgate CSJ, Vijay V, Scotton W, Wakerley BR, Matthews TD, Ansons A, Hickman SJ, Benzimra J, Rick C, Singhal R, Tahrani AA, Brock K, Frew E, Sinclair AJ. Effectiveness of bariatric surgery vs community weight management intervention for the treatment of idiopathic intracranial hypertension: a randomized clinical trial. JAMA Neurol. 2021;76:678–686. 5. Beuker C, Wankner MC, Thomas C, Strecker JK, Schmidt-Pogoda A, Schwindt W, Schulte-Mecklenbeck A, Gross C, Wiendl H, Barth PJ, Eckert B, Meinel TR, Arnold M, Schaumberg J, Kruger S, Deb-Chatterji M, Magnus T, Rother J, Minnerup J. Characterization of extracranial giant cell arteritis with intracranial involvement and its rapidly progressive subtype. Ann Neurol. 2021;90:118–128. 6. Chen BS, Meyer BI, Saindane AM, Bruce BB, Newman NJ, Biousse V. Prevalence of incidentally detected signs of intracranial hypertension on magnetic resonance imaging and their association with papilledema. JAMA Neurol. 2021;78:718–725. Mac Grory B, Schrag M, Biousse V, Furie KL, Gerhard-Herman M, Lavin PJ, Sobrin L, Tjoumakaris SI, Weyand CM, Yaghi S; American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Council on Peripheral Vascular Disease. Management of central retinal artery occlusion: a scientific statement from the American Heart Association. Stroke. 2021;52:e282–e294. Purpose: Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that causes severe visual loss and is a harbinger of further cerebrovascular and cardiovascular events. There is a paucity of scientific information on the appropriate management of CRAO, with most strategies based on observational literature and expert opinion. In this scientific statement, we critically appraise the literature on CRAO and provide a framework within which to consider acute treatment and secondary prevention. Methods: We performed a literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case–control studies, case reports, clinical guidelines, Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 review articles, basic science articles, and editorials concerning the management of CRAO. We assembled a panel comprising experts in the fields of vascular neurology, neuro-ophthalmology, vitreoretinal surgery, immunology, endovascular neurosurgery, and cardiology, and document sections were divided among the writing group members. Each member received an assignment to perform a literature review, synthesize the data, and offer considerations for practice. Multiple drafts were circulated among the group until consensus was achieved. Results: Acute CRAO is a medical emergency. Systems of care should evolve to prioritize early recognition and triage of CRAO to emergency medical attention. There is considerable variability in management patterns among practitioners, institutions, and subspecialty groups. The current literature suggests that treatment with intravenous t-PA may be effective. Patients should undergo urgent screening and treatment of vascular risk factors. There is a need for highquality, randomized clinical trials in this field. COMMENTS It is always nice to have guidelines from respected societies and here is one from the American Heart Association 413 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary (AHA) on the management of central retinal artery occlusion (CRAO). Kudos to Biousse and Lavin for representing the neuro-ophthalmology community. To be completely honest, there is not much new in the guidelines that we already do not know or do. I think all of us now treat an acute CRAO as a stroke with immediate referral to an emergency department or stroke center. For treatment of the visual loss, this is what the guidelines state: • Intravenous t-PA may be considered in patients who have disabling visual deficits and who otherwise meet criteria for systemic t-PA after a thorough benefit/risk discussion with the affected patient. • In centers capable of deploying endovascular therapy, intra-arterial t-PA may be considered in patients with disabling visual deficits at early time points, especially if they are not candidates for intravenous t-PA. This consideration comes with the strong caveat that, at present, IAT is an unproven therapy and should be considered only in light of the devastating visual outcome associated with CRAO. • There is no compelling evidence that conservative treatments for CRAO are effective, and trends in the observational literature suggest that ocular massage, anterior chamber paracentesis, and hemodilution may be harmful. • There is a need for a pragmatic, randomized, placebocontrolled, double-blind clinical trial comparing t-PA with placebo as treatment for patients with CRAO presenting at early time points. Future research should explore biomarkers of retinal viability that may complement existing, time-based approaches to thrombolytic therapy. The use of the novel thrombolytic agent tenecteplase and intra-arterial t-PA at early time points should be explored in future studies. —M. Tariq Bhatti, MD This article provides an excellent summary of CRAO, including epidemiology, pathophysiology, workup, prognosis, and current state of treatment. They quote a survey study that found 39% of patients would accept a risk of stroke and 37% would accept a risk of death for a 3-fold chance of improving vision to a 20/100 level, even with a normal contralateral eye. If the contralateral eye is impaired, 80% would accept such risks. With that in mind, the most important immediate need is to determine whether early intravenous thrombolysis is truly effective and to educate the public and physicians to evaluate patients with CRAO within minutes to hours of symptom onset. The authors note that there are currently 3 clinical trials in Europe studying IV t-PA or tenecteplase in patients within 4.5 hours of CRAO onset. I agree with their statement, “Until a fully powered efficacy trial has been completed, we feel that there is equipoise in the utility of intravenous tPA for CRAO, and the decision to use this therapy rests on a thorough discussion between the treating specialist and the affected patient, 414 which includes an acknowledgment of the limitations inherent in the literature to date.” —Mark L. Moster, MD Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020;588:124–129. Abstract: Aging is a degenerative process that leads to tissue dysfunction and death. A proposed cause of aging is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to DNA methylation patterns over time form the basis of aging clocks, but whether older individuals retain the information needed to restore these patterns—and, if so, whether this could improve tissue function—is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity. Using the eye as a model CNS tissue, here, we show that the ectopic expression of Oct4 (also known as Pou5f1), Sox2, and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—which can be accessed to improve tissue function and promote regeneration in vivo. COMMENTS Mark, throw away your “Just for Men” hair dye because I think I just found you the fountain of youth! I am not going to pretend to understand everything these brilliant scientists did, but the bottom line is that by using an optic nerve crush adult mouse model and a rodent glaucoma model, retinal ganglion cells (RGCs) were regenerated by reprogramming cells using 3 specific factors altering epigenetic factors associated with aging (“methylation clock”). The amazing part of all this is that RGC regeneration could be induced weeks after optic nerve injury. —M. Tariq Bhatti, MD If you do not understand it all, I do not have a chance! The authors relate that in mammals, damaged RGCs of embryos and neonates can regenerate axons, but this capacity is lost within days after birth. By intravitreal Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary injection in mice of genetically engineered adeno-associated virus that induced 3 of the ‘Yamanaka factors,’ a group of 4 transcription factors (Oct4, Sox2, Klf4, and c-Myc) that can trigger mature cell types to adopt an immature state, they were able to regenerate RGCs. By not using c-Myc, they were able to avoid genetic changes that can lead to the growth of tumors. This is very exciting work that brings us closer to restoring vision in optic neuropathies. —Mark L. Moster, MD CI, 23,121 to 2461 mg) of prednisone over 1 year (i.e., 5.3 mg/d per patient, P = 0.03). The number of serious adverse events did not differ significantly between the slow-tapering vs rapid-tapering group (13 [22%] vs 21 [36%], P = 0.15). Conclusions and Relevance: In patients with moderate-tosevere generalized MG who require high-dose prednisone with azathioprine therapy, rapid tapering of prednisone seems to be feasible, well tolerated, and associated with a good outcome. COMMENTS Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B; MYACOR Study Group. Comparison of corticosteroid tapering regimens in myasthenia gravis: a randomized clinical trial. JAMA Neurol. 2021;78:426–433. Importance: The tapering of prednisone therapy in generalized myasthenia gravis (MG) presents a therapeutic dilemma; however, the recommended regimen has not yet been validated. Objective: To compare the efficacy of the standard slowtapering regimen of prednisone therapy with a rapidtapering regimen. Design: From June 1, 2009, to July 31, 2013, a multicenter, parallel, single-blind randomized trial was conducted to compare 2 regimens of prednisone tapering. Data analysis was conducted from February 18, 2019, to January 23, 2020. A total of 2,291 adults with a confirmed diagnosis of moderate-to-severe generalized MG at 7 specialized centers in France were assessed for eligibility. Interventions: The slow-tapering arm included a gradual increase of the prednisone dose to 1.5 mg/kg every other day and a slow decrease once minimal manifestation status of MG was attained. The rapid-tapering arm consisted of immediate high-dose daily administration of prednisone, 0.75 mg/kg, followed by an earlier and rapid decrease once improved MG status was attained. Azathioprine, up to a maximum dose of 3 mg$kg21$day21, was prescribed for all participants. Main Outcomes and Measures: The primary outcome was attainment of minimal manifestation status of MG without prednisone at 12 months and without clinical relapse at 15 months. Intention-to-treat analysis was conducted. Results: Of the 2,291 patients assessed, 2,086 did not fulfill the inclusion criteria, 87 declined to participate, and 1 patient registered after trial closure. A total of 117 patients (58 in the slow-tapering arm and 59 in the rapidtapering arm) were selected for inclusion by MG specialists and were randomized. The population included 62 men (53%); the median age was 65 years (interquartile range, 35–69 years). The proportion of patients having met the primary outcome was higher in the rapid-tapering vs slowtapering arm (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% confidence interval [CI], 1.64–7.97; P , 0.001) after adjusting for center and thymectomy. The rapid-tapering regimen allowed sparing of a mean of 1,898 mg (95% Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 Despite the long history of myasthenia gravis (MG), there still remains a lot we still need to learn about its medical management in particular corticosteroid therapy. This multicenter, single-blind randomized trial compared the efficacy of a slow prednisone tapering scheduling with a rapid-tapering schedule in patients with seropositive generalized MG being treated with azathioprine. The authors state that typically the prednisone dosage in the treatment of moderate-to-severe MG is a gradual increase to 0.75 mg/kg on alternate days and then decreased down until the patient hits the target of minimal manifestation status (MMS). It is clear from the change in the exclusion criteria (delay of prednisone interruption from 2 months to 1 month) and extension of the study by 12 months that there were some challenges in the recruitment of patients. Ultimately, 117 patients were enrolled with 113 completing the study. There were 58 patients in the slow-tapering group and 59 patients in the rapid-tapering group. The median age of the cohort was 65 years (interquartile range 35–69 years). The primary outcome was the proportion of participants having reached MMS without prednisone at 12 months and having not relapsed or taken prednisone between months 12 and 15. The slow-tapering group received the following prednisone regimen: The initial dose was 10 mg and was increased by increments of 10 mg every 2 days up to 1.5 mg/kg of body weight on alternate days without exceeding 100 mg. This dose was maintained until MMS was reached and then reduced by 10 mg every 2 weeks until a dosage of 40 mg was reached, with subsequent slowing of the taper to 5 mg monthly. The rapid-tapering group received the following complex prednisone regimen: Prednisone was immediately started at 0.75 mg/kg/ day. If the patient reached MMS at 1 month, the dose of prednisone was reduced by 0.1 mg/kg every 10 days up to 0.45 mg/kg/day, then 0.05 mg/kg every 10 days up to 0.25 mg/kg/day, and then in decrements of 1 mg by adjusting the duration of the decrements according to the participant’s weight with the aim of achieving complete cessation of corticosteroid therapy within the planned time frame (i.e., 126–140 days for this third stage of 415 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary tapering). Second, if the state of MMS was not reached at 1 month but the participant had improved according to the Myasthenia Gravis Foundation of America (MGFA) classification postintervention status, the prednisone dose was decreased by 0.1 mg/kg every 20 days until the dose of 0.45 mg/kg/day was achieved, then 0.05 mg/kg every 20 days up to 0.25 mg/kg/day, and then by decrements of 1 mg as described in the preceding paragraph. If the participant reached MMS during this tapering process, the tapering of prednisone was similar to the sequence described in the first stage. Third, if MMS was not reached and the participant had not improved, the initial dose was maintained for the first 3 months; beyond that time, a decrease in the prednisone dose was undertaken as follows: Decrease of 0.1 mg/kg every 20 days up to 0.45 mg/kg/day, then by 0.05 mg/kg every 20 days up to 0.25 mg/kg/day, and after which the prednisone dose was not reduced further. However, if the participant improved, the tapering of prednisone followed the sequence described in the second category. The proportion of patients having met the primary outcome was higher in the rapid-tapering group (23 [39%] vs 5 [9%]), with a risk ratio of 3.61 (95% CI, 1.64–7.97; P , 0.001) after adjusting for center and thymectomy. There was no significant difference in the prednisonerelated complications between the 2 groups (91% slowtapering group vs 93% rapid-tapering group). A few more outcomes worthy of note include no difference in the percentage of patients worsening between the 2 groups (50% slow-tapering group vs 54% rapid-tapering group), no statistical difference in time to achieve MMS (132 days slowtapering group vs 155 days rapid-tapering group, P = 0.10), and the cumulated mean dose of prednisone was significantly less in the rapid-tapering group (10, 562 mg slowtapering group vs 8, 724 mg rapid-tapering group) with a cumulative dose reduction over 1 year of 5 mg/day in favor of the rapid-tapering group. I think an important caveat to this study is that it looked at a very focused group of patients with generalized MG treated with azathioprine. In fact, of the 2,291 patients, the authors assessed only a total of 117 patients who were enrolled in the study, which calculates to only 5%! Therefore, I am not sure how generalizable the results of this study are to other patients with MG , in particular ocular MG. —M. Tariq Bhatti, MD It is good to know that tapering prednisone more rapidly was at least as good as the slower regimen. However, as you point out, this study, which had difficulty in recruitment, is on a limited population with moderate-to-severe generalized MG, all of whom were treated with azathioprine. How it relates to the patients I might treat with prednisone alone is unclear. —Mark L. Moster, MD 416 Mollan SP, Mitchell JL, Ottridge RS, Aguiar M, Yiangou A, Alimajstorovic Z, Cartwright DM, Grech O, Lavery GG, Westgate CSJ, Vijay V, Scotton W, Wakerley BR, Matthews TD, Ansons A, Hickman SJ, Benzimra J, Rick C, Singhal R, Tahrani AA, Brock K, Frew E, Sinclair AJ. Effectiveness of bariatric surgery vs community weight management intervention for the treatment of idiopathic intracranial hypertension: a randomized clinical trial. JAMA Neurol. 2021;76:678–686. Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse. Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. Design, Setting, and Participants: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the United Kingdom between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. Interventions: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). Main Outcomes and Measures: The primary outcome was the change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. Results: Of the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, 26.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, 29.5 to 22.4 cm CSF; P = 0.001) and at 24 months (adjusted mean [SE] difference, 28.2 [2.0] cm CSF; 95% CI, 212.2 to 24.2 cm CSF; P , 0.001) compared with the CWM arm. In the per-protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, 27.2 [1.8] cm CSF; 95% CI, 210.6 to 23.7 cm CSF; P , 0.001) and at 24 months (adjusted mean [SE] difference, 28.7 [2.0] cm CSF; 95% CI, 212.7 to 24.8 cm CSF; P , 0.001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, 221.4 [5.4] kg; 95% CI, 232.1 to 210.7 kg; P , 0.001) and at 24 months (adjusted mean [SE] difference, 226.6 [5.6] kg; 95% CI, 237.5 Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary to 215.7 kg; P , 0.001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2–14.4; P = 0.04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0– 17.9; P = 0.006) in the bariatric surgery arm. Conclusions and Relevance: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention regarding sustained disease remission. COMMENTS This article reports the results of the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT). Sixty-six women aged 18–55 years with a body mass index of at least 35 kg/m2, papilledema, normal MRI (except for signs of IIH), lumbar puncture with opening pressure .25 cm H20, and without prior success at weight loss were randomized to bariatric surgery vs community weight management with paid participation in Weight Watchers. It is no surprise that bariatric surgery would result in more weight loss than a Weight Watchers regimen with variable patient compliance. It also follows that there would be more of a decrease in intracranial pressure (ICP) with the increased weight loss. One would expect better visual outcomes with greater weight loss. However, the vision was quite good in this cohort, and the study was not powered to detect such benefit. Some limitations are pointed out by Deb Friedman in an accompanying editorial(1). For instance, 14 (42.4%) participants randomized to the weight management arm never attended a Weight Watchers session, 2 participants withdrew from the study, and 2 participants underwent bariatric surgery on their own. She suggests there may be a frustration with dietary management in patients with IIH or that the patients may have enrolled in the IIH:WT hoping to be randomized to the bariatric surgery arm, and their disappointment contributed to low adherence. She also points out that a post hoc analysis showed a greater reduction in the use of acetazolamide, topiramate, and preventative headache medications in the surgical group, noting that migraine is the most common headache type in IIH and that it is linked to obesity. Our colleague, Susan Mollan et al, provide good evidence favoring bariatric surgery over community weight management. What would be a next step is to study whether bariatric surgery leads to improvement in visual outcome in patients with more moderate visual loss. —Mark L. Moster, MD 1. Friedman DI. Bariatric surgery in patients with idiopathic intracranial hypertension-the silver bullet? JAMA Neurol. 2021;78:652–654. Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 This is a wonderful contribution to the literature, but I have a question, why use the difference in the ICP between the 2 groups as the primary outcome? I ask this question because what does ICP really tell us in IIH? As you know in the IIH treatment trial (IIHTT), the primary outcome was the change in perimetric mean deviation (PMD) from baseline to month 6 (1). In fact, the IIHTT found that the opening pressure at baseline was not associated with PMD or clinical symptoms, including headache disability, and there was no statistically significant difference in the opening pressure between nonfailures and treatment failures (2,3). I wonder if an outcome to have measured was the total dose of acetazolamide used between the 2 groups, as is often performed in giant cell arteritis treatment trials. —M. Tariq Bhatti, MD 1. NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee, Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, Katz DM, Keltner JL, Schron EB, Kupersmith MJ. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014;311:1641–1651. 2. Friedman DI, Quiros PA, Subramanian PS, Mejico LJ, Gao S, McDermott M, Wall M; the NORDIC IIHTT Study Group. Headache in idiopathic intracranial hypertension: findings from the Idiopathic Intracranial Hypertension Treatment Trial. Headache. 2017;57:1195–1205. 3. Wall M, Falardeau J, Fletcher WA, Granadier RJ, Lam BL, Longmuir RA, Patel AD, Bruce BB, He H, McDermott MP; NORDIC Idiopathic Intracranial Hypertension Study Group. Risk factors for poor visual outcome in patients with idiopathic intracranial hypertension. Neurology. 2015;85:799–805. Beuker C, Wankner MC, Thomas C, Strecker JK, Schmidt-Pogoda A, Schwindt W, SchulteMecklenbeck A, Gross C, Wiendl H, Barth PJ, Eckert B, Meinel TR, Arnold M, Schaumberg J, Kruger S, Deb-Chatterji M, Magnus T, Rother J, Minnerup J. Characterization of extracranial giant cell arteritis with intracranial involvement and its rapidly progressive subtype. Ann Neurol. 2021;90:118– 128. Objective: The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement. Methods: In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17) and with intracranial atherosclerosis (n = 25) served as controls. Results: The erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with intracranial involvement and in 16 patients (100%) without intracranial involvement (P = 0.02). Headache was complained by 15 patients 417 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary (50.0%) with intracranial involvement and 13 patients (76.5%) without intracranial involvement (P = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, by contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at follow-up in these patients was 4 (interquartile range [IQR] = 2.0–6.0), and 4 patients (36.4%) died. The vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course. Interpretation: Typical characteristics of GCA, headache, and an elevated ESR are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets. COMMENTS It is estimated that 4% of patients with giant cell arteritis (GCA) have involvement of intracranial arteries and may present with stroke. This study from 5 neurology departments over an undisclosed number of years characterized 31 such patients. They compared characteristics of patients with GCA with intracranial involvement with patients with GCA without intracranial involvement and with patients with atherosclerotic disease. Patients with intracranial involvement less frequently presented with headache (50.0% vs 76.5%, P = 0.03) or an elevated erythrocyte sedimentation rate (ESR; 69.2% vs 100%, P = 0.02). Ischemic strokes occurred in 80.6% of patients, 67.7% infratentorial, 32.3% supratentorial, and 22.6% in both. Bilateral strokes occurred in 45% of patients. Vertebral artery stenosis was seen in 84% of patients, of whom 31% had occlusion and 58% were bilateral. The location of involvement differed from patients with atherosclerotic disease, which primarily affected the vertebral artery after the takeoff of the posterior inferior cerebellar artery (PICA). Patients with GCA had multiple areas of involvement below and above the PICA origin. Carotid artery involvement was mainly bilateral carotid siphon stenosis. A rapidly progressive course with recurrent ischemic events was seen in 38% of patients. The median time from first symptom to stroke was 2 months, but 10% of patients had stroke at the onset of GCA symptoms. I remember vividly a patient from neurology residency who presented with bilateral hemispheric infarcts and was mute. I met the patient on my neuro-ophthalmology rotation with my mentor, Tom Slamovits, who made the 418 diagnosis of GCA which was not even considered by our own neurology service. Over the years, I have been convinced that many strokes due to GCA have been misdiagnosed as atherosclerotic for some of the reasons pointed out by the authors of this article. First, atherosclerosis is extremely common in the age group of the patient with GCA and may coexist. Second, stroke may be an early GCA manifestation, so the systemic clues may not be prominent. In addition, 31% in this series had a normal ESR and 17% a normal C-reactive protein. Problems with this study include its retrospective nature, small size, and the diagnosis made with the American College of Rheumatology (ACR) criteria, including 18 temporal artery biopsies (TAB) and 13 by noninvasive means. Nonetheless, it provides useful information and should heighten our awareness of the uncommon presentation of GCA with cerebrovascular disease. —Mark L. Moster, MD I want to emphasize why the diagnosis of GCA based on the ACR is not appropriate. The ACR criteria were developed to differentiate GCA from other vasculitides (1). If you recall, the 5 ACR criteria were age $50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, ESR $50 mm/hour, and a positive TAB. The presence of $3 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. The Wills Eye group highlighted the poor clinical validity of the ACR criteria when they found that 25.7% of their patients with a positive TAB would not have been diagnosed with GCA using the ACR criteria (2). —M. Tariq Bhatti, MD 1. Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW, Masi AT, McShane DJ, Mills JA, Wallace SL, Zvaifler NJ. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33:1122–1128. 2. Murchison AP, Gilbert ME, Bilyk JR, Eagle RC Jr, Pueyo V, Sergott RC, Savino PJ. Validity of the American College of Rheumatology criteria for the diagnosis of giant cell arteritis. Am J Ophthalmol. 2012;154:722–729. Chen BS, Meyer BI, Saindane AM, Bruce BB, Newman NJ, Biousse V. Prevalence of incidentally detected signs of intracranial hypertension on magnetic resonance imaging and their association with papilledema. JAMA Neurol. 2021;78:718–725. Importance: MRI signs of intracranial hypertension (IH) are traditionally associated with idiopathic intracranial hypertension (IIH), but these signs are also detected among Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary individuals with primary headaches and among asymptomatic individuals without papilledema. Objective: To examine the prevalence of MRI signs of IH among consecutive outpatients undergoing brain MRI for any clinical indication and to explore their association with papilledema. Design, Setting, and Participants: This prospective crosssectional study of outpatients undergoing brain MRI at 1 outpatient imaging facility was conducted between August 1, 2019, and March 31, 2020, with ocular fundus photographs taken concurrently. Radiographic images from consecutive adult patients who were undergoing brain MRI and able to participate in fundus photography were analyzed for MRI signs of IH. A univariate analysis using either Fisher exact tests or t tests was performed. Main Outcomes and Measures: Prevalence of MRI signs of IH and prevalence of papilledema detected on ocular fundus photographs. Radiographic signs of IH included empty sella, optic nerve head protrusion, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, enlarged Meckel caves, cephaloceles, cerebellar tonsillar descent, and bilateral transverse venous sinus stenosis. Results: A total of 388 patients were screened for eligibility; of those, 92 patients were excluded (58 declined participation, 16 were unable to consent, 14 were unable to complete fundus photography, and 4 completed MRI and fundus photography twice, so their second set of findings was removed). Among the 296 patients included in the study, the median age was 49.5 years (interquartile range, 37.8– 62.0 years) and 188 patients (63.5%) were female. The most common indication for MRI was surveillance of a brain neoplasm (82 patients [27.7%]). Investigations of headaches (26 patients [8.8%]) and disorders of intracranial pressure (4 patients [1.4%]) were uncommon. At least 1 radiographic sign of IH was present in 145 patients (49.0%). Among 296 total study patients, 98 patients (33.1%) had empty sella, 47 patients (15.9%) had enlarged Meckel caves, 32 patients (10.8%) had increased perioptic cerebrospinal fluid, 23 patients (7.8%) had optic nerve tortuosity, 2 patients (0.7%) had scleral flattening, and 4 patients (1.4%) had cephaloceles. Bilateral transverse venous sinus stenosis was present in 6 of 198 patients (3.0%). Five patients (1.7%) had papilledema. Compared with patients without papilledema, those with papilledema had a significantly higher body mass index and history of IIH, in addition to an increased prevalence of empty sella, optic nerve tortuosity, and transverse venous sinus stenosis detected on MRI. The prevalence of papilledema increased from 2.8% among patients with at least 1 MRI sign of IH to 40.0% among patients with 4 or more MRI signs of IH. Conclusions and Relevance: MRI signs of IH were common among patients undergoing brain MRI in this study but rarely associated with papilledema. The management of patients with incidentally detected signs of IH likely does not require systematic lumbar puncture unless concerning symptoms or papilledema are present. Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 413-419 COMMENTS We often referred patients with coincidental discovery of signs of intracranial hypertension (IH) on MRI, sometimes after already having had a lumbar puncture. This prospective study from our Emory colleagues of consecutive patients undergoing MRI found that 49% of patients had at least 1 finding that has been seen in chronic IH. All these patients had fundus photography at the time of MRI, and of those with 1 MRI sign of IH, only 2.8% had papilledema in comparison with 40.0% of those with 4 or more signs of IH. Among 296 total study patients, 33.1% had empty sella, 15.9% had enlarged Meckel caves, 10.8% had increased perioptic cerebrospinal fluid (CSF), 7.8% had optic nerve tortuosity, 0.7% had scleral flattening, and 1.4% had cephaloceles. Bilateral transverse venous sinus stenosis was present in 6 of 198 patients (3.0%). This article aptly points out that in patients with prior IH that has resolved MRI signs of IH persist even after the intracranial pressure normalizes. Signs related to bony erosion, including empty sella and enlarged Meckel cave, are likely to persist, whereas posterior scleral flattening, increased perioptic CSF, and optic nerve tortuosity may improve. A potential problem with this study was that 82 patients had a history of brain tumor, so they may have had prior IH that resolved, with MRI findings that persisted. However, the authors point out that their findings were unchanged when those 82 patients were excluded. The authors conclude that with findings suggestive of IH, proceeding with clinical evaluation, including funduscopic examination, is preferable to proceeding with lumbar puncture (LP). In contrast to the debate going on in the current Journal of Neuro-Ophthalmology about LP in patients with typical IIH, I think we can all agree with this recommendation. —Mark L. Moster, MD I assessed this article on June 5, 2021, from the JAMA Neurology website, and it already had 4,000 views, which speaks to its interest and clinical relevance. As you, I agree with the authors’ conclusion that a funduscopic examination is preferable before performing a LP, but what this study does not tell us is how many of the 291 patients without papilledema had increased CSF opening pressure (a.k.a. idiopathic intracranial hypertension without papilledema). —M. Tariq Bhatti, MD 419 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
Date | 2021-09 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Source | Journal of Neuro-Ophthalmology, September 2021, Volume 41, Issue 3 |
Collection | Neuro-Ophthalmology Virtual Education Library - Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890 |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s6nm7yp3 |
Setname | ehsl_novel_jno |
ID | 2033186 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s6nm7yp3 |