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BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a rare autoimmune disease characterized by inflammation of small- to medium-sized blood vessels (vasculitis). We described the 3 causes of GPA-associated optic neuropathy (compressive, inflammatory, or ischemic) and analyzed initial and final visual acuities (VAs) in each group, which could potentially help prognosticate visual outcomes depending on the etiology of optic neuropathy. METHODS: This was a retrospective chart review of patients who were diagnosed with GPA-associated optic neuropathy and were seen in the Department of Ophthalmology at Mayo Clinic in Rochester, Minnesota. Only patients who met the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology GPA classification criteria were included. RESULTS: A total of 12 patients with GPA-associated optic neuropathy were identified. The etiology of the optic neuropathy was compressive in 6 patients, inflammatory in 4 patients, and ischemic in 3 patients. One patient had compressive optic neuropathy initially, then presented with GPA-related optic neuritis years later. Four patients in the compressive optic neuropathy group had orbital masses requiring orbitotomy for debulking, and the remaining 2 patients had compression from pachymeningitis. Average logarithm of the minimum angle of resolution (logMAR) VA at optic neuropathy onset was 1.50, 1.50, and 0.67 (Snellen equivalent 20/600, 20/600, and 20/100, respectively). At the last follow-up, average logMAR VA was 0.91, 1.73, and 1.10 (Snellen equivalent 20/160, 20/1,000, and 20/250, respectively) for each group. CONCLUSION: Visual outcomes were variable, with compressive and inflammatory optic neuropathies showing improvement in 4 eyes and worsening in 3 eyes in total. Patients with ischemic optic neuropathy from GPA were either stable or worsened over the course of the disease.
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OBJECTIVES: To describe papillitis as a clinical phenotype of IgLON5 autoimmunity. METHODS: We retrospectively reviewed patients with IgLON5 autoimmunity who had optic neuropathy, optic neuritis, or optic disc edema. Sera from patients with recurrent papillitis were tested for IgLON5 antibodies. RESULTS: We found two elderly males presenting with papillitis in the presence of IgLON5 antibodies. CSF pleocytosis was present and partial vision improvement occurred in one patient despite immunotherapy. Sera from 18 patients with recurrent papillitis were negative for IgLON5 antibodies. CONCLUSION: Papillitis could be a manifestation of IgLON5 disease, with or without accompanying cognitive, sleep, and movement disorders.
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Neurite Óptica , Papiledema , Masculino , Humanos , Idoso , Autoimunidade , Estudos Retrospectivos , Neurite Óptica/complicações , Nervo Óptico , Moléculas de Adesão Celular Neuronais/uso terapêuticoRESUMO
BACKGROUND: Optic neuritis (ON) is the most common optic neuropathy in young adults. MRI is reported to have a high sensitivity for ON. Higher signal strengths of MRI may enhance resolution and lead to better detection of ON. We sought to compare the sensitivity of 3.0 Tesla (T) MRI to that of 1.5 T MRI in detecting acute demyelinating ON. METHODS: A retrospective chart review was performed on patients with a clinical diagnosis of optic neuritis at Mayo Clinic Health System from January 2010 to April 2020. Among 1,850 patients identified, 126 patients met the eligibility criteria. Exclusion criteria comprised questionable or alternative diagnosis, diagnosis of ON before the study period, eye examinations performed elsewhere, or absence of fat-saturated head and orbits MRIs performed locally within 30 days of symptom onset. Gadolinium contrast enhancement, T2 hyperintensity, and the radiologic diagnosis of ON were recorded by a neuro-radiologist who was masked to the clinical history and the magnet strength of the MRI. RESULTS: Fifty-three patients (42.1%) had 3.0 T MRI, and 73 patients (57.9%) had 1.5 T MRI. Overall, 88.9% (112/126) of patients were determined to have a positive MRI for ON. The radiographic sensitivity for ON was higher in the 3.0 T group compared with the 1.5 T group (98.1% vs 82.2%, respectively [ P = 0.004]). The frequency of gadolinium enhancement was found to be greater in the 3 T group compared with the 1.5 T group (98.1% vs 76.7%, respectively [ P < 0.001]). T2 hyperintensity was also more often seen in the 3.0 T group compared with the 1.5 T group (88.7% vs 68.5%, respectively [ P = 0.01]). CONCLUSIONS: 3.0 T MRI is more sensitive than 1.5 T MRI in detecting ON. This finding suggests that 3.0 T MRI is a preferred imaging modality for the confirmation of ON.
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Gadolínio , Neurite Óptica , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética/métodos , Neurite Óptica/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemAssuntos
Retina/diagnóstico por imagem , Neovascularização Retiniana/etiologia , Vasos Retinianos/diagnóstico por imagem , Síndrome de Susac/complicações , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , Angiofluoresceinografia/métodos , Fundo de Olho , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neovascularização Retiniana/diagnóstico , Síndrome de Susac/diagnósticoRESUMO
PURPOSE: We detail a case of cobalt toxicity with visual and systemic complications, review the pathogenic process for the optic neuropathy and retinopathy, and discuss the controversy of metallic hip prosthesis. OBSERVATIONS: A 59-year-old female with a history of multiple left hip arthroplasties presented to our clinic with bilateral visual loss. The year prior, she had failure of the hip implant necessitating revision surgery with placement of a chrome-cobalt head. A few months after surgery, she began experiencing blurred and "white, spotty" vision in both eyes in addition to hypothyroidism, cardiomyopathy and neuropathy. The possibility of the patient's symptoms being due to cobalt toxicity from her hip prosthesis was proposed and she was found to have a serum cobalt level >1000 µg/L (normal 0-0.9 ng/mL). Visual acuity was 20/600 in the right and 20/800 in the left eye. There was bilateral temporal optic disc pallor. Goldmann visual field testing demonstrated bilateral central scotomas, optical coherence tomography (OCT) showed severe ganglion cell layer-inner plexiform layer (GCLIPL) thinning and multifocal electroretinography (mfERG) demonstrated decreased amplitudes in both eyes. She underwent a total hip revision arthroplasty with extensive debridement of "black sludge" found within a pseudocapsule. Four days after surgery, cobalt serum levels had significantly decreased to 378 ng/mL. One month after surgery, she had significant improvement in visual acuity (20/150 right eye, 20/250 left eye), Goldmann visual field testing, and mfERG. OCT showed retinal nerve fiber thinning and persistent GCLIPL thinning in both eyes. CONCLUSIONS AND IMPORTANCE: Excessive cobalt levels can result in systemic toxicity leading to visual changes, peripheral neuropathy, hearing loss, cognitive deficits, cardiomyopathy and hypothyroidism. In recent years it has become apparent that cobalt toxicity can be associated with metal-on-metal total hip arthroplasty, or the grinding effects of retained ceramic particles from a fractured ceramic head on a cobalt-chromium femoral head prosthesis.
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BACKGROUND: The UK ALLR3 (R3) regimen has been adopted to treat pediatric relapsed acute lymphoblastic leukemia (ALL) by many centers in the United States and has become a preferred therapeutic backbone for testing novel agents in clinical trials. A detailed toxicity profile of this platform has not previously been reported. The toxicity and response rates for its use beyond first relapse are unknown. PROCEDURES: We performed a multi-institutional, retrospective study including children with relapsed ALL treated with the R3 reinduction chemotherapy backbone block 1 across five pediatric centers. Data were extracted from medical records and analyzed. RESULTS: Fifty-nine patients were included in the study, including 16 patients with ≥2nd relapse. Ninety-seven percent of patients experienced at least one Grade ≥3 nonhematologic adverse event (AE). Grade 3 or higher infection was reported in 90% of patients. Other nonhematologic Grade ≥3 AEs included electrolyte abnormalities, elevation in hepatic enzymes, and pain. Eighty-five percent of patients achieved a complete remission (CR). There were no significant differences in the incidence of AEs, CR rate, and rate of minimal residual disease negativity between patients with 1st or ≥2nd relapse. CONCLUSION: Our study confirmed that R3 block 1 is a highly active reinduction regimen in childhood relapsed ALL. However, it was associated with a high incidence of severe toxicities, particularly infection. The toxicity profiled in our report should be used to inform optimal supportive care and future clinical trial design with the R3 backbone, particularly when new agents are combined with this regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Indução , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos RetrospectivosRESUMO
OBJECTIVE: The goal of this study was to develop dually radiolabeled peptides for simultaneous imaging of cancer cell localization by targeting the α(v)ß(3) integrin and their pathophysiology by targeting the activity of the proteolytic enzyme MMP2, involved in the metastatic process. METHODS: A hybrid peptide c(RGDfE)K(DOTA)PLGVRY containing an RGD motif for binding to the α(v)ß(3)integrin, a metal chelator (DOTA) for radiolabeling with [(64)Cu], and the MMP2 substrate cleavage sequence PLGVRY with terminal tyrosine for labeling with [(123)I] was synthesized, labeled with [(64)Cu] and [(123)I], and evaluated in vitro as a potential imaging agent. RESULTS: The peptide was synthesized and labeled with [(64)Cu] and [(123)I] with 300 and 40 µCi/µg (542 and 72.2 mCi/µmol) specific activities, respectively, and radiochemical purity of >98%. c(RGDfE)K(DOTA)PLGVRY demonstrated high affinity for α(v)ß(3) integrins (Kd=83.4+13.2 nM) in both substrate competition and cell binding assays. c(RGDfE)K(DOTA)PLGVRY peptide, but not the scrambled version, c(RGDfE)K(DOTA)GRPLVY was specifically cleaved by MMP2. CONCLUSIONS: These results demonstrate the feasibility of developing dually radiolabeled peptides for the simultaneous imaging of cancer cells and their pathophysiologic activity.