Publications by authors named "Bart K Chwalisz"

38 Publications

The Treatment of Myelin Oligodendrocyte Glycoprotein Antibody Disease: A State-of-the-Art Review.

J Neuroophthalmol 2022 Aug 9. Epub 2022 Aug 9.

Department of Neurology (BKC, ML), Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts; and Department of Ophthalmology (BKC), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.

Background: Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is an important etiology of neurologic morbidity and specifically, atypical, and relapsing optic neuritis. This review summarizes acute treatment and long-term prevention approaches in MOGAD.

Evidence Acquisition: PubMed and Google Scholar databases were manually searched and reviewed.

Results: We review the evidence base for acute treatment of MOGAD with corticosteroids and adjunct therapies, such as intravenous immunoglobulin (IVIg) and plasma exchange. We discuss the utility of prolonged corticosteroid tapering after the acute attack. We then summarize the commonly used disease-modifying treatments for relapsing MOGAD, including chronic low-dose corticosteroids, classic antirheumatic immune suppressants, biologic agents, and IVIg.

Conclusions: While acute MOGAD attacks are usually treated with high-dose IV corticosteroids, longer oral corticosteroid tapers may prevent rapid relapse. Multiple long-term treatment strategies are being employed in recurrent MOGAD, with IVIg is emerging as probably the most effective therapy.
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http://dx.doi.org/10.1097/WNO.0000000000001684DOI Listing
August 2022

Treatment outcomes of first-ever episode of severe optic neuritis.

Mult Scler Relat Disord 2022 Jul 2;66:104020. Epub 2022 Jul 2.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology, Mayo Clinic Alix School of Medicine, Rochester MN.

Background: Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear.

Methods: We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up.

Results: Of the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004).

Conclusion: In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.
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http://dx.doi.org/10.1016/j.msard.2022.104020DOI Listing
July 2022

Clinical and neuroradiologic characteristics in varicella zoster virus reactivation with central nervous system involvement.

J Neurol Sci 2022 06 16;437:120262. Epub 2022 Apr 16.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, United States of America; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America. Electronic address:

Objective: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS).

Methods: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS.

Results: The median age was 71 years [IQR 51.5-76]; 21 (57%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65%); median CSF white blood cell count was 11 [IQR 2-23] cells/μL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29%) CSF and 8/9 (89%) ocular samples. Clinical involvement included the optic nerve in 12 (32%), other cranial nerves in 20 (54%), brain parenchyma in 12 (32%) and spinal cord or nerve roots in 4 (11%). Twenty-seven/28 immunocompetent patients' MRIs were available for review (96%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN.

Conclusion: OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation.
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http://dx.doi.org/10.1016/j.jns.2022.120262DOI Listing
June 2022

Pseudotumor Cerebri Syndrome With COVID-19: A Case Series.

J Neuroophthalmol 2022 Apr 27. Epub 2022 Apr 27.

Division of Neuro-ophthalmology (LM, EF, BKC), Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts; Division of Neuro-ophthalmology (MAB), Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Neurobiology (DHB, SRD), Harvard Medical School, Boston, Massachusetts; Division of Neuro-ophthalmology (SP), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Neurology (BKC), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1097/WNO.0000000000001467DOI Listing
April 2022

Posterior Ischemic Optic Neuropathy in the Setting of Cocaine-Induced Orbital and Sinonasal Inflammation.

Ophthalmic Plast Reconstr Surg 2022 Apr 25. Epub 2022 Apr 25.

Ophthalmic Plastic Surgery Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, U.S.A.

Intranasal cocaine abuse can lead to significant sinus and orbital complications, including optic neuropathy. A 46-year-old man with a history of recurrent cocaine-induced sino-orbital inflammation and infection with bony destruction presented with acute, painless, vision loss. Examination revealed no light perception vision. MRI of the orbits demonstrated new restricted diffusion of the right optic nerve on diffusion-weighted imaging and apparent diffusion coefficient sequences, consistent with posterior ischemic optic neuropathy. This is the first among cases of cocaine-induced optic neuropathy in the literature to illustrate ischemic changes on MRI in the optic nerve, highlighting the utility of diffusion-weighted imaging/apparent diffusion coefficient sequences when optic neuropathy is suspected and further suggesting an underlying ischemic etiology in similar cases.
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http://dx.doi.org/10.1097/IOP.0000000000002181DOI Listing
April 2022

Optic Perineuritis Associated With Cryptococcal Meningitis Presenting With a "Hot Orbit" in a Patient With Chronic Lymphocytic Leukemia.

J Neuroophthalmol 2022 06 23;42(2):272-277. Epub 2022 Mar 23.

Department of Ophthalmology (DLL, BKC, EDG), Mass Eye and Ear, Boston, Massachusetts; Department of Ophthalmology (EKT), Boston Medical Center, Boston, Massachusetts; Department of Pathology (MYL), Boston VA Medical Center, Boston, Massachusetts; Department of Optometry (JEK), Boston VA Medical Center, Boston, Massachusetts; Department of Radiology (NJF), Stanford University Medical Center, Stanford, California; Department of Ophthalmology (DRL), Boston VA Medical Center, Boston, Massachusetts; Division of Ophthalmic Plastic and Reconstructive Surgery (DRL), Massachusetts Eye and Ear, Boston, Massachusetts; Division of Neuro-Immunology (BKC), Massachusetts General Hospital, Boston, Massachusetts; Department of Ophthalmology (EDG), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; and Picower Institute for Learning and Memory (EDG), Massachusetts Institute of Technology, Cambridge, Massachusetts.

Abstract: A 75-year-old man presented with 3 days of progressive left retro-orbital pain, eyelid swelling, tearing, and pain with extraocular movement. His medical history was significant for type II diabetes mellitus and chronic lymphocytic leukemia, stable on no therapy since diagnosis 8 years prior. The initial examination was significant for diffuse restriction of left ocular motility, marked lid edema, and mild dyschromatopsia. Computed tomography demonstrated asymmetric left periorbital soft tissue swelling and intraconal fat stranding with an irregular left optic nerve sheath complex and clear paranasal sinuses. He was hospitalized for orbital cellulitis and treated empirically with broad-spectrum intravenous antibiotics, but his visual acuity declined over the ensuing 2 days. Subsequent MRI demonstrated left-greater-than-right circumferential optic nerve sheath enhancement, and leptomeningeal enhancement. An orbital biopsy demonstrated monoclonal B-cell lymphocyte aggregation, whereas a lumbar puncture was positive for Cryptococcus antigen with subsequent demonstration of abundant Cryptococcus by Papanicolaou stain. The final diagnosis was optic perineuritis secondary to cryptococcal meningitis presenting with orbital inflammation. Although his clinical course was complicated by immune reconstitution inflammatory syndrome, symptoms and signs of optic neuropathy ultimately resolved after 1 month of intensive antifungal therapy.
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http://dx.doi.org/10.1097/WNO.0000000000001538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124683PMC
June 2022

Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report and Review of the Literature.

J Neuroophthalmol 2022 03 4;42(1):e56-e62. Epub 2022 Jan 4.

Ophthalmic Plastic Surgery (VDL, MKY), Department of Ophthalmology, Massachusetts Eye and Ear/Harvard Medical School, Boston, Massachusetts; Department of Radiology (MM), Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Neuro-ophthalmology (BKC), Department of Ophthalmology, Massachusetts Eye and Ear/Harvard Medical School, Boston, Massachusetts; and Department of Neurology (BKC), Massachusetts General Hospital / Harvard Medical School, Boston, Massachusetts.

Background: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype.

Methods: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD).

Results: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust.

Conclusion: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.
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http://dx.doi.org/10.1097/WNO.0000000000001400DOI Listing
March 2022

Neuroradiologic Imaging of Neurologic and Neuro-Ophthalmic Complications of Coronavirus-19 Infection.

J Neuroophthalmol 2021 12;41(4):452-460

Department of Radiology (M. Marsiglia), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurology (BKC), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology (BKC), Massachusetts Eye & Ear, Harvard Medical School, Boston, Massachusetts; and Department of Radiology/Division of Neuroradiology (M. Maher), University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.

Background: To review the literature and provide a summary of COVID-19-related neurologic and neuro-ophthalmic complications.

Methods: The currently available literature was reviewed on PubMed and Google Scholar using the following keywords for searches: CNS, Neuro-Ophthalmology, COVID-19, SARS-CoV-2, coronavirus, optic neuritis, pseudotumor cerebri, Acute Disseminated Encephalomyelitis, posterior reversible encephalopathy syndrome (PRES), meningitis, encephalitis, acute necrotizing hemorrhagic encephalopathy, and Guillain-Barré and Miller Fisher syndromes.

Results: Neuroradiologic findings of neurologic and neuro-ophthalmologic complications in relationship to COVID-19 infection were reviewed. Afferent visual pathway-related disorders with relevant imaging manifestations included fundus nodules on MRI, papilledema and pseudotumor cerebri syndrome, optic neuritis, Acute Disseminated Encephalomyelitis, vascular injury with thromboembolism and infarct, leukoencephalopathy, gray matter hypoxic injury, hemorrhage, infectious meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and PRES. Efferent visual pathway-related complications with relevant imaging manifestations were also reviewed, including orbital abnormalities, cranial neuropathy, Guillain-Barré and Miller Fisher syndromes, and nystagmus and other eye movement abnormalities related to rhombencephalitis.

Conclusion: COVID-19 can cause central and peripheral nervous system disease, including along both the afferent and efferent components of visual axis. Manifestations of disease and long-term sequela continue to be studied and described. Familiarity with the wide variety of neurologic, ophthalmic, and neuroradiologic presentations can promote prompt and appropriate treatment and continue building a framework to understand the underlying mechanism of disease.
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http://dx.doi.org/10.1097/WNO.0000000000001454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582975PMC
December 2021

Chronic Relapsing Inflammatory Optic Neuropathy (CRION).

Curr Opin Ophthalmol 2021 11;32(6):521-526

Department of Ophthalmology, Division of Neuro-Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1097/ICU.0000000000000804DOI Listing
November 2021

Case 292: Lyme Neuroborreliosis.

Radiology 2021 08;300(2):484-488

From the Departments of Ophthalmology (V.P.D., K.A.A.D., B.K.C.) and Radiology (K.L.R.), Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA 02114; and Department of Neurology, Neuro-Ophthalmology Service, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (B.K.C.).

History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed.
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http://dx.doi.org/10.1148/radiol.2021201715DOI Listing
August 2021

Case 22-2021: A 64-Year-Old Woman with Cognitive Impairment, Headache, and Memory Loss.

N Engl J Med 2021 Jul;385(4):358-368

From the Department of Neurology, Brigham and Women's Hospital (S.B.), the Departments of Radiology (R.G.G.), Neurology (B.K.C.), and Pathology (S.N.C.), Massachusetts General Hospital, and the Departments of Neurology (S.B., B.K.C.), Radiology (R.G.G.), and Pathology (S.N.C.), Harvard Medical School - all in Boston.

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http://dx.doi.org/10.1056/NEJMcpc2103460DOI Listing
July 2021

Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors.

J Immunother Cancer 2021 07;9(7)

Harvard Medical School, Boston, Massachusetts, USA.

Expanding the US Food and Drug Administration-approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%-12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.
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http://dx.doi.org/10.1136/jitc-2021-002890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291304PMC
July 2021

Clinical Reasoning: A 28-Year-Old Woman With Vision Loss and an Unusual Gait.

Neurology 2021 11 29;97(18):e1860-e1865. Epub 2021 Jun 29.

Department of Ophthalmology (J.C.D., B.K.C.), Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; and Department of Neurology (B.K.C., C.D.S.), Massachusetts General Hospital, Boston, MA.

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http://dx.doi.org/10.1212/WNL.0000000000012446DOI Listing
November 2021

Afferent and Efferent Neuro-Ophthalmic Complications of Coronavirus Disease 19.

J Neuroophthalmol 2021 06;41(2):154-165

Department of Ophthalmology and Visual Sciences (AKT), University of Iowa Hospital and Clinics, University of Iowa Carver College of Medicine, Iowa City, Iowa; Departments of Ophthalmology and Neurology (MD), New York- Presbyterian Hospital, Weill Cornell Medical College, New York City, New York; Department of Ophthalmology (BKC), Massachusetts Eye & Ear; and Department of Neurology (BKC), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Purpose: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19) documented in the literature thus far.

Methods: The PubMed and Google Scholar databases were searched using the keywords: Neuro-Ophthalmology, COVID-19, SARS-CoV-2, and coronavirus. A manual search through reference lists of relevant articles was also performed.

Results/conclusions: The literature on COVID-associated neuro-ophthalmic disease continues to grow. Afferent neuro-ophthalmic complications associated with COVID-19 include optic neuritis, papillophlebitis, papilledema, visual disturbance associated with posterior reversible encephalopathy syndrome, and vision loss caused by stroke. Efferent neuro-ophthalmic complications associated with COVID-19 include cranial neuropathies, Miller Fisher syndrome, Adie's pupils, ocular myasthenia gravis, nystagmus and eye movement disorders. Proposed mechanisms of neurologic disease include immunologic upregulation, vasodilation and vascular permeability, endothelial dysfunction, coagulopathy, and direct viral neurotropism. When patients present to medical centers with new onset neuro-ophthalmic conditions during the pandemic, COVID-19 infection should be kept on the differential.
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http://dx.doi.org/10.1097/WNO.0000000000001276DOI Listing
June 2021

Case 292.

Radiology 2021 04;299(1):234-236

From the Departments of Ophthalmology (V.P.D., K.A.A.D., B.K.C.) and Radiology (K.L.R.), Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA 02114; and Department of Neurology, Neuro-Ophthalmology Service, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (B.K.C.).

History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed (Figs 1, 2).
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http://dx.doi.org/10.1148/radiol.2021201712DOI Listing
April 2021

Neuro-ophthalmic Complications of Immune-Checkpoint Inhibitors.

Semin Ophthalmol 2021 May 27;36(4):241-249. Epub 2021 Feb 27.

Department of Ophthalmology, Massachusetts Eye & Ear/Harvard Medical School, Boston, MA, USA.

Immune checkpoint inhibitors (ICIs) have revolutionized the field of oncology by modulating the immune cell-cancer cell interaction and thereby promoting immune system disinhibition in order to target several types of malignancies. There are three classes of immune checkpoint inhibitors (ICIs): anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1), and anti-programmed cell death ligand-1 (PD-L1).It is not uncommon for physicians across all specialties to encounter a patient with a history of malignancy and ICI exposure, necessitating familiarity with their potential complications. In this review article, we discuss the most common immune-related adverse events (irAEs) pertaining to the central and peripheral nervous systems and their potential afferent and efferent neuro-ophthalmic manifestations. Early recognition and treatment of these irAEs, and discontinuation of the offending ICI are all critical steps to prevent morbidity and mortality.
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http://dx.doi.org/10.1080/08820538.2021.1890796DOI Listing
May 2021

Ptosis as Clinical Presentation in a Patient With Emery-Dreifuss Muscular Dystrophy Type 5.

J Neuroophthalmol 2021 09;41(3):e333-e334

Department of Ophthalmology (KAAD, VPD, BKC) Massachusetts Eye and Ear Infirmary/Harvard Medical School, Neuro-Ophthalmology Service, Boston, Massachusetts; Department of Ophthalmology (EDG), Boston Children's Hospital/Harvard Medical School, Boston, Massachusetts; Department of Brain and Cognitive Sciences (EDG, BKC), Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts; and Department of Neurology (BKC), Massachusetts General Hospital/Harvard Medical School, Boston Massachusetts.

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http://dx.doi.org/10.1097/WNO.0000000000001187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373992PMC
September 2021

Case 6-2021: A 65-Year-Old Man with Eye Pain and Decreased Vision.

N Engl J Med 2021 Feb;384(8):745-753

From the Department of Neurology, Beth Israel Deaconess Medical Center (M.A.B.), the Departments of Neurology (B.K.C.), Radiology (J.M.R.), Neuro-oncology (I.C.A.-R.), and Pathology (L.R.M.), Massachusetts General Hospital, and the Departments of Neurology (B.K.C.), Radiology (J.M.R.), Neuro-oncology (I.C.A.-R.), and Pathology (L.R.M.), Harvard Medical School - all in Boston.

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http://dx.doi.org/10.1056/NEJMcpc2027089DOI Listing
February 2021

Why They Took the Oath: A Spotlight on Resident Sacrifice During the Pandemic.

J Neuroophthalmol 2021 03;41(1):1-5

Departments of Ophthalmology (SE, MD), and Neurology (SB, MD), Weill Cornell Medical College, New York, New York; Department of Ophthalmology (BKC), Massachusetts Eye & Ear, Boston, Massachusetts; and Department of Neurology (BKC), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1097/WNO.0000000000001202DOI Listing
March 2021

Case 26-2020: A Woman with Altered Mental Status and Left-Sided Weakness. Reply.

N Engl J Med 2021 01;384(1):92

Massachusetts General Hospital, Boston, MA.

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http://dx.doi.org/10.1056/NEJMc2030849DOI Listing
January 2021

Nelson Syndrome: Clival Invasion of Corticotroph Pituitary Adenoma Resulting in Alternating Sixth Nerve Palsies.

J Neuroophthalmol 2021 03;41(1):114-118

Division of Neuro-Ophthalmology (VPD, KAAD, BKC), Massachusetts Eye and Ear/Harvard Medical School, Boston, Massachusetts; and Departments of Radiology (OR), Pathology (SNC), and Neurology (BKC), Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts.

Abstract: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed.
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http://dx.doi.org/10.1097/WNO.0000000000001141DOI Listing
March 2021

A multi-center case series of sarcoid optic neuropathy.

J Neurol Sci 2021 01 19;420:117282. Epub 2020 Dec 19.

Mayo Clinic, Department of Neurology, 200 1st St. SW, Rochester, MN, USA. Electronic address:

Objective: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes.

Methods: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis.

Results: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up.

Conclusions: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.
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http://dx.doi.org/10.1016/j.jns.2020.117282DOI Listing
January 2021

Hemorrhagic Papilledema Secondary to Craniopharyngioma.

JAMA Ophthalmol 2020 10 8;138(10):e200880. Epub 2020 Oct 8.

Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.0880DOI Listing
October 2020

Neuro-ophthalmic manifestations of Susac syndrome.

Curr Opin Ophthalmol 2020 Nov;31(6):495-502

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary.

Purpose Of Review: This review discusses general features and organ-specific presentations of Susac syndrome as well as diagnosis and treatment.

Recent Findings: Latest literature regarding demographics, new diagnostic modalities such as optical coherence tomography and treatment options for Susac syndrome are discussed in detail in this review, summarizing the most recent updated information.

Summary: Susac syndrome is a rare, underdiagnosed, and often misdiagnosed disease that can lead to severe complications such as deafness, vision loss, dementia, and death. It involves the central nervous system and may mimic other neurological and neuro-ophthalmological diseases.
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http://dx.doi.org/10.1097/ICU.0000000000000713DOI Listing
November 2020

Neuro-ophthalmic manifestations of coronavirus disease 19.

Curr Opin Ophthalmol 2020 Nov;31(6):489-494

Department of Ophthalmology, Massachusetts Eye & Ear.

Purpose Of Review: To provide a summary of the neuro-ophthalmic manifestations of coronavirus disease 19 (COVID-19), documented in the literature thus far.

Recent Findings: A small but growing literature documents cases of new onset neuro-ophthalmic disease, in the setting of COVID-19 infection. Patients with COVID-19 have experienced acute onset vision loss, optic neuritis, cranial neuropathies, and Miller Fisher syndrome. In addition, COVID-19 increases the risk of cerebrovascular diseases that can impact the visual system.

Summary: The literature on COVID-19 continues to evolve. Although COVID-19 primarily impacts the respiratory system, there are several reports of new onset neuro-ophthalmic conditions in COVID-infected patients. When patients present with new onset neuro-ophthalmic issues, COVID-19 should be kept on the differential. Testing for COVID-19 should be considered, especially when fever or respiratory symptoms are also present. When screening general patients for COVID-19-associated symptoms, frontline physicians can consider including questions about diplopia, eye pain, pain with extraocular movements, decreased vision, gait issues, and other neurologic symptoms. The presence of these symptoms may increase the overall probability of viral infection, especially when fever or respiratory symptoms are present. More research is needed to establish a causal relationship between COVID-19 and neuro-ophthalmic disease, and better understand pathogenesis.
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http://dx.doi.org/10.1097/ICU.0000000000000707DOI Listing
November 2020

Reply to: Cluster headache by orbital myositis. Comment: Orbital myositis triggering oxygen-responsive cluster headache.

Cephalalgia 2020 12 26;40(14):1680. Epub 2020 Sep 26.

1866Massachusetts Eye and Ear Infirmary - Ophthalmology, Boston, MA, USA.

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http://dx.doi.org/10.1177/0333102420961561DOI Listing
December 2020

Case 26-2020: A 60-Year-Old Woman with Altered Mental Status and Weakness on the Left Side.

N Engl J Med 2020 Aug;383(8):764-773

From the Departments of Neurology (A.B.S., B.K.C., S.S.M.) and Radiology (R.G.G.), Massachusetts General Hospital, and the Departments of Neurology (A.B.S., B.K.C., S.S.M.) and Radiology (R.G.G.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc2004976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449228PMC
August 2020

Disease of the Year: COVID-19 and Its Neuro-ophthalmic Complications.

J Neuroophthalmol 2020 09;40(3):283-284

Department of Ophthalmology, Massachusetts Eye and Ear and Massachusetts General Hospital (BKC), Harvard Medical School, Boston Massachusetts; and Departments of Ophthalmology and Neurology (MJD), Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York.

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http://dx.doi.org/10.1097/WNO.0000000000001046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382415PMC
September 2020

Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy-Related Inflammation.

JAMA Neurol 2020 10;77(10):1261-1269

J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston.

Importance: Cerebral amyloid angiopathy-related inflammation (CAA-ri), a distinct subtype of cerebral amyloid angiopathy, is characterized by an autoimmune reaction to cerebrovascular β-amyloid deposits. Outcomes and response to immunosuppressive therapy for CAA-ri are poorly understood.

Objective: To identify clinical, neuroimaging, laboratory, pathologic, or treatment-related associations with outcomes after an episode of CAA-ri.

Design, Setting, And Participants: A retrospective cohort study of prospectively identified individuals who presented from July 3, 1998, to November 27, 2017, with a median follow-up of 2.7 years (interquartile range, 1.0-5.5 years). The study included 48 consecutive patients with CAA-ri meeting diagnostic criteria who had at least 1 disease episode and subsequent outcome data. No patients refused or were excluded.

Exposures: Prespecified candidate variables were immunosuppressive therapies, cerebrospinal fluid pleocytosis, magnetic resonance imaging findings of recent infarcts or contrast enhancement, and histopathologic evidence of vessel wall inflammation.

Main Outcomes And Measures: Clinical improvement and worsening were defined by persistent changes in signs or symptoms, radiographic improvement by decreased subcortical foci of T2 hyperintensity or T1 enhancement, and radiographic worsening by increased subcortical T2 hyperintensity, T1 enhancement, or infarcts. Disease recurrence was defined as new-onset clinical symptoms associated with new imaging findings.

Results: The 48 individuals in the study included 29 women and had a mean (SD) age of 68.9 (9.9) years. Results of presenting magnetic resonance imaging revealed that 10 of 29 patients with CAA-ri (34%) had T1 contrast enhancement, 30 of 32 (94%) had subcortical T2 hyperintensity (22 of 30 [73%] asymmetric), 7 of 32 (22%) had acute or subacute punctate infarcts, and 27 of 31 (87%) had microbleeds. Immunosuppressive treatments after first episodes included corticosteroids (33 [69%]), cyclophosphamide (6 [13%]), and mycophenolate (2 [4%]); 14 patients (29%) received no treatment. Clinical improvement and radiographic improvement were each more likely in individuals treated with an immunosuppressive agent than with no treatment (clinical improvement: 32 of 34 [94%] vs 7 of 14 [50%]; odds ratio, 16.0; 95% CI, 2.72-94.1; radiographic improvement: 24 of 28 [86%] vs 4 of 14 [29%]; odds ratio, 15.0; 95% CI, 3.12-72.1). Recurrence was less likely if CAA-ri was treated with any immunosuppressant agent than not (9 of 34 [26%] vs 10 of 14 [71%]; hazard ratio, 0.19; 95% CI, 0.07-0.48). When controlling for treatment, no variables were associated with outcomes aside from an association between APOE ɛ4 and radiographic improvement (odds ratio, 4.49; 95% CI, 1.11-18.2).

Conclusions And Relevance: These results from a relatively large series of patients with CAA-ri support the effectiveness of immunosuppressive treatment and suggest that early treatment may both improve the initial disease course and reduce the likelihood of recurrence. These results raise the possibility that early blunting of CAA-ri and the autoimmune response may have long-term benefits for the subsequent disease course.
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http://dx.doi.org/10.1001/jamaneurol.2020.1782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309570PMC
October 2020

Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

J Neuroophthalmol 2021 Jun;41(2):217-223

Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.

Background: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility.

Methods: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed.

Results: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient.

Conclusions: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.
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http://dx.doi.org/10.1097/WNO.0000000000000926DOI Listing
June 2021
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