Astrocytic outer retinal layer thinning is not a feature in AQP4-IgG seropositive neuromyelitis optica spectrum disorders.

BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.

Retinal Optical Coherence Tomography in Neuromyelitis Optica.

BACKGROUND AND OBJECTIVES: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts. METHODS: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA). RESULTS: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 µm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 µm, p < 0.001). GCIP layer loss (-22.7 µm) after the first ON was higher than after the next (-3.5 µm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC. DISCUSSION: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO).

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

A personal journey in advocacy.

Over the past decade, neurology advocacy has caught the attention of neurologists feeling increasingly frustrated about the health care environment in which they practice. We describe our experience in practicing advocacy at the national and local levels. Neurologists can participate in many levels of advocacy to benefit their patients and their profession.

Clinical course and prognosis of trochlear nerve schwannomas.

PURPOSE: To delineate the disease course and prognosis of patients with mass lesions of the fourth nerve presumed to be schwannomas. DESIGN: Nonrandomized retrospective case series. PARTICIPANTS: Thirty-seven consecutive cases of presumed trochlear nerve schwannoma from 9 tertiary university neuro-ophthalmology centers. METHODS: Cases were collected, and their clinical characteristics on presentation and follow-up are described. Inclusion criteria were brain magnetic resonance imaging (MRI) with a lesion suggestive of a schwannoma along the course of the fourth nerve. Exclusion criteria were other causes of fourth nerve palsy, such as congenital, traumatic or microvascular; normal (or lack of) initial brain MRI; lack of adequate clinical information; and disappearance of the lesion on subsequent follow-up brain MRI. MAIN OUTCOME MEASURES: Demographics of patients, presence of neurofibromatosis, symptoms on presentation, vertical deviation, lesion size (on presentation and follow-up), length of follow-up, and outcomes of treatment for lesions or diplopia. RESULTS: Seven patients were excluded and of the 30 patients included in our series, patients were predominantly male (77%) with a mean age of 51 years (range 9-102 years). In contrast with prior case reports, almost all of our cases had a fourth nerve palsy on presentation (29/30), often isolated. Mean follow-up was 3.1 years (range 0.2 months to 11.1 years). There was no significant difference between initial and follow-up lesion size (4.4 vs. 5 mm) for patients who did not receive treatment of lesions (P = 0.36). Only 3 patients underwent neurosurgical resection and an additional patient received gamma-knife radiotherapy. The majority of patients (24/30) did not pursue strabismus surgery for vertical diplopia. CONCLUSIONS: Patients with isolated fourth nerve palsy and small lesions of the fourth nerve have a good prognosis and should be followed with serial MRI scans without neurosurgical intervention unless they develop signs of brain stem compression. Most patients with diplopia and benign fourth nerve lesions typical of trochlear nerve schwannoma can adapt with either prism spectacles or no treatment at all, although strabismus surgery can be successful.

Life-threatening polyneuropathy heralding renal cell carcinoma.

OBJECTIVE: To report the occurrence of life-threatening polyneuropathy in association with renal cell carcinoma. METHODS: Case report and review of the medical literature. RESULTS: A 65-year-old man developed a fulminant, life-threatening sensory motor polyneuropathy several months before renal cell carcinoma was identified. Dramatic symptomatic improvement ensued after treatment with intravenous immunoglobulin, although the patient succumbed to complications of the tumor years later. CONCLUSIONS: Chronic sensory motor polyneuropathy is a known paraneoplastic syndrome associated with renal cell carcinoma. This report emphasizes that in rare conditions, the polyneuropathy could take an acute demyelinating form, which is important for clinicians to recognize.